Research Annual Report 2010

Transcription

1 Research Annual Report 2010 Molecular Medicine (MM) Solid Pharmacogenetics tumors between bench and bed Improving Clinical and accuracy experimental and therapeutic neuroendocrinology ratio radiation oncology Hyperthermia: Regulation of calcium a treatment and bone for cancer metabolism Photodynamic Regulation of therapy bioactivity of thyroid hormone Neuro-oncology Signalling in reproduction and pain and ageing Pathophysiological Localisation, detection aspects and radionuclide and treatment therapy of gastro-intestinal of various diseases diseases Surgical The musculoskeletal trauma and the system development and tissue-engineering of tumour recurrence in orthopaedics and otorhinolaryngology Innovative Regulation tumor of follicle model development, development/tumor oocyte and vasculature/tumor endometrial embryo targeting/locoregional quality control Clinical Pathophysiology and experimental of pediatric aspects endocrine, of urological metabolic tumors and renal diseases Gynaecological Malignant transformation oncology; basics, of hematopoietic epidemiology stem and cells: clinical pathophysiology aspects and development of therapy Developmental Hematopoiesis: biology; regulation pathophysiology of the proliferation of the and newborn differentiation of hematopoietic progenitor cells Experimental Molecular determinants therapeutical of therapy approaches response in inflammatory and outcome dermatoses in childhood and cancer cutaneous oncology Translational Lymphoid differentiation genomics and and proteomics immunodeficiencies of cancer Translational Immune regulation pharmacology and autoimmunity Neoplastic Diagnosis, classification lesions and chronic and treatment inflammatation evaluation of the of leukemias gastrointestinal and malignant tract lymphomas 11771, B&T Ontwerp en advies (

2 Research Annual Report 2010 Molecular Medicine (MM) Solid tumors between bench and bed Improving accuracy and therapeutic ratio in radiation oncology Hyperthermia: a treatment for cancer Photodynamic therapy Neuro-oncology and pain Pathophysiological aspects and treatment of gastro-intestinal diseases Surgical trauma and the development of tumour recurrence Innovative tumor model development/tumor vasculature/tumor targeting/locoregional control Clinical and experimental aspects of urological tumors Gynaecological oncology; basics, epidemiology and clinical aspects Developmental biology; pathophysiology of the newborn Experimental therapeutical approaches in inflammatory dermatoses and cutaneous oncology Translational genomics and proteomics of cancer Translational pharmacology Neoplastic lesions and chronic inflammatation of the gastrointestinal tract 11771, B&T Ontwerp en advies (

3 Research Annual Report 2010 Molecular Medicine (MM) Liverspecific immunopathology; mechanism and therapeutic modulation Human virus infections: immunity, therapy and epidemiology Infections due to bacteria, fungi and parasites: diagnosis, molecular mechanisms, epidemiology, therapy and prevention Clinical research in infectious diseases in adults Renal insufficiency and organ transplantation Cell biological and pathophysiological investigations on pulmonary diseases Neuromuscular and Neuroinflammatory Disorders Organ transplantation Genitourinary tract disorders in children Disorders of the gastrointestinal tract in childhood Clinical, epidemiological and basic research of infectious diseases and immunological diseases in children 11771, B&T Ontwerp en advies (

4 EMC MM Pharmacogenetics Programme in brief design The focus of this program is on molecular markers that can predict the effectiveness or the risk of adverse reactions of therapeutic interventions. In particular, the contribution of genetic factors in the drug metabolism is investigated. Translational research is performed to define and evaluate the clinical significance of genetic polymorphisms in drug metabolizing enzymes (o.a. CYP450s, UGTs, TPMT and NAT genes), drug transporters (OATPS, OATS, ABC-Transporters) and drug targets (a.o. Folate-Dependant Emzymes). Drug classes include immuno-suppressives, anti-depressants, anti-cancer drugs, anaesthetics, anti-arrhytmics, anti-viral drugs, anti-coagulation drugs, proton pump inhibitors, opioids and anti-rheumatoïd drugs. In addition, genetic and metabolic factors are investigated that determine the level of plasma homocysteine and its deleterious effect on methylation reactions. Key figures Department SP1 SP2 SP3 SP4 Sptot T1 T2 T3 Ttot IS FS OP Ptot clinical chemistry 3, ,53 internal medicine 0, ,3 medical oncology Total 4, , Artikel/Letter to the editor Bangma, C.H., Schaik, R.H.N. van, Blijenberg, B.G., Roobol, M.J., Lilja, H. & Stenman, UH (2010). On the use of prostatespecific antigen for screening of prostate cancer in European Randomised Study for Screening of Prostate Cancer. European Journal of Cancer, 46(17), Becker, M.L., Visser, L.E., Schaik, R.H.N. van, Hofman, A., Uitterlinden, A.G. & Stricker, B.H.C. (2010). Influence of genetic variation in CYP3A4 and ABCB1 on dose decrease or switching during simvastatin and atorvastatin therapy. Pharmacoepidemiology and Drug Safety, 19(1), Becker, M.L., Visser, L.E., Schaik, R.H.N. van, Hofman, A., Uitterlinden, A.G. & Stricker, B.H.C. (2010). Interaction between polymorphisms in the OCT1 and MATE1 transporter and metformin response. Pharmacogenetics Genomics, 20(1), Blonk, M.I., Velde, N. van der, Bemt, P.M.L.A. van den, Schaik, R.H.N. van & Cammen, T.J.M. van der (2010). CYP2D6*4, CYP3A5*3 and ABCB1 3435T polymorphisms and drug-related falls in elderly people. Pharmacy World & Science, 32(1), Boer, D.P., Rijke, Y.B. de, Hop, W.C.J., Cransberg, K. & Dorresteijn, E.M. (2010). Reference values for serum creatinine in children younger than 1 year of age. Pediatric Nephrology, 25, Bol, J.M. van der, Jong, F.A. de, Schaik, R.H.N. van, Sparreboom, A., Fessem, M.A.C. van, Geijn, F.E. van de, Daele, P.L.A. van, Verweij, J., Sleijfer, S. & Mathijssen, R.H.J. (2010). Effects of Mannose-Binding Lectin Polymorphisms on Irinotecan- Induced Febrile Neutropenia. Oncologist, 15(10), Crop, M.J., Rijke, Y.B. de, Verhagen, P.C.M.S., Cransberg, K. & Zietse, R. (2010). Diagnostic Value of Urinary Dysmorphic Erythrocytes in Clinical Practice. Nephron Clinical Practice, 115(3), C203-C212. Deenik, W., Holt, B. van der, Janssen, J.J.W.M., Chu, IWT, Valk, P.J.M., Ossenkoppele, G.J., Heiden, I.P. van der, Sonneveld, P., Schaik, R.H.N. van & Cornelissen, J.J. (2010). Polymorphisms in the multidrug resistance gene MDR1 (ABCB1) predict for molecular resistance in patients with newly diagnosed chronic myeloid leukemia receiving high-dose imatinib. Blood, 116(26), Gensburger, O, Schaik, R.H.N. van, Picard, N., Meur, Y. Le, Rousseau, A, Woillard, JB, Gelder, T. van & Marquet, P (2010). Polymorphisms in type I and II inosine monophosphate dehydrogenase genes and association with clinical outcome in patients on mycophenolate mofetil. Pharmacogenetics Genomics, 20(9), Henrichs, J., Schokking, J.J., Schenk, JJ, Ghassabian, A., Schmidt, H.G., Visser, T.J., Hooijkaas, H., Muinck Keizer-Schrama, S.M.P.F., Hofman, A., Jaddoe, V.W.V.K., Visser, W., Steegers, E.A.P., Verhulst, F.C., Rijke, Y.B. de & Tiemeier, H.W. (2010). Maternal Thyroid Function during Early Pregnancy and Cognitive Functioning in Early Childhood: The Generation R Study. Journal of Clinical Endocrinology and Metabolism, 95(9), Jansen, F.H., Schaik, R.H.N. van, Kurstjens, J, Horninger, W, Klocker, H, Bektic, J, Wildhagen, M.F., Roobol, M.J., Bangma, C.H. & Bartsch, G. (2010). Prostate-Specific Antigen (PSA) Isoform p2psa in Combination with Total PSA and Free PSA Improves Diagnostic Accuracy in Prostate Cancer Detection. European Urology, 57(6), Jonge, R. de, Brouwer, R., Graaf, M.T. de, Luitwieler, RL, Fleming, C, Frankrijker-Merkestijn, M. de, Sillevis Smitt, P.A.E., Boonstra, J.G. & Lindemans, J. (2010). Evaluation of the new body fluid mode on the Sysmex XE-5000 for counting leukocytes and erythrocytes in cerebrospinal fluid and other body fluids. Clinical Chemistry and Laboratory Medicine, 48(5), Lammers, L.A., Mathijssen, R.H.J., Gelder, T. van, Bijl, M.J., Graan, A.M. de, Seynaeve, C., Fessem, M. van, Berns, E.M.J.J., Vulto, A.G. & Schaik, R.H.N. van (2010). The impact of CYP2D6-predicted phenotype on tamoxifen treatment outcome in patients with metastatic breast cancer. British Journal of Cancer, 103(6),

5 Luin, M van, Ende, M.E. van der, Richter, C., Visser, M., Faraj, D, Ven, A. van de, Gelinck, L.B.S., Kroon, F., Wit, FW, Schaik, R.H.N. van, Kuks, PFM & Burger, D.M. (2010). Lower atovaquone/proguanil concentrations in patients taking efavirenz, lopinavir/ritonavir or atazanavir/ritonavir. Aids, 24(8), Meesters, R.J.W., Cornelissen, R., Klaveren, R.J. van, Jonge, R. de, Boer, E., Lindemans, J. & Luider, T.M. (2010). A new ultrafast and high-throughput mass spectrometric approach for the therapeutic drug monitoring of the multi-targeted anti-folate pemetrexed in plasma from lung cancer patients. Analytical and Bioanalytical Chemistry, 398(7-8), Payne, DA, Mamotte, CDS, Gancberg, D, Pazzagli, M, Schaik, R.H.N. van, Schimmel, H & Rousseau, F. (2010). Nucleic acid reference materials (NARMs): definitions and issues. Clinical Chemistry and Laboratory Medicine, 48(11), Pekelharing, J.M., Hauss, O, Jonge, R. de, Lokhoff, J, Sodikromo, J, Spaans, M, Brouwer, R., Lathouder, S. de & Hinzmann, R (2010). Haematology reference intervals for established and novel parameters in healthy adults. Diagnostic Perspectives, 1, Rakhmanina, N.Y., Anker, J.N. van den, Soldin, SJ, Schaik, R.H.N. van, Mordwinkin, N & Neely, MN (2010). Can Therapeutic Drug Monitoring Improve Pharmacotherapy of HIV Infection in Adolescents? Therapeutic Drug Monitoring, 32(3), Re, M. Del, Paolo, A. Di, Schaik, R.H.N. van, Bocci, G, Simi, P, Falcone, A & Danesi, R. (2010). Dihydropyrimidine dehydrohenase polymorphisms and fluoropyrimidine toxicity: ready for routine clinical application within personalized medicine. EPMA Journal, 1, Rotte, M.C.F.J. de, Luime, J.J., Bulatovic, M, Hazes, J.M.W., Wulffraat, N.M. & Jonge, R. de (2010). Do snapshot statistics fool us in MTX pharmacogenetic studies in arthritis research? Rheumatology, 49(6), Ruiter, R. de, Bijl, M.J., Schaik, R.H.N. van, Berns, P.M.J.J., Hofman, A., Coebergh, J.W.W., Noord, C. van, Visser, L.E. & Stricker, B.H.C. (2010). CYP2C19*2 polymorphism is associated with increased survival in breast cancer patients using tamoxifen. Pharmacogenomics, 11(10), Russcher, H., Herwaarden, AE van, Boesten, L.S.M., Kemna, MS, Curvers, J, Heijboer, AC, Engbers-Buijtenhuis, P & Deckers, MML (2010). Klinische chemie voor iedereen: het Wikipedia-project. Nederlands Tijdschrift voor Klinische Chemie, 35, Sandberg, Y., Rood, P.P.M., Russcher, H., Zwaans, J.J.M., Weigel, J.D. & Daele, P.L.A. van (2010). Falsely elevated lactate in severe ethylene glycol intoxication. Netherlands Journal of Medicine, 68(7-8), Schenk, P.W., Vliet, M. van, Mathot, R.A.A., Gelder, T. van, Vulto, A.G., Fessem, M.A.C. van, Rij, SVV, Lindemans, J., Bruijn, J.A. & Schaik, R.H.N. van (2010). The CYP2C19(star)17 genotype is associated with lower imipramine plasma concentrations in a large group of depressed patients. Pharmacogenomics Journal, 10(3), Schiettecatte, J, Russcher, H., Anckaert, E, Mees, M., Leeser, B, Tirelli, AS, Fiedler, GM, Luthe, H, Denk, B & Smitz, J (2010). Multicenter evaluation of the first automated Elecsys sflt-1 and PlGF assays in normal pregnancies and preeclampsia. Clinical Biochemistry, 43(9), Siemes, C., Visser, L.E., Jong, F.H. de, Coebergh, J.W.W., Uitterlinden, A.G., Hofman, A., Stricker, B.H.C. & Schaik, R.H.N. van (2010). Cytochrome P450 3A gene variation, steroid hormone serum levels and prostate cancer-the Rotterdam Study. Steroids, 75(12), Part of book - abstract Gysel, D. van, Schaik, R.H.N. van & Oranje, A.P. (2010). Mastocytosis. In J Harper, AP Oranje & N Prose (Eds.), Textbook of pediatric dermatology (pp. 75). New York: Blackwell Publishing. 71

6 EMC MM Clinical and experimental neuroendocrinology Programme in brief design A. Studies on the regulation of hormone secretion by the normal pituitary gland as well as by human pituitary tumours in vivo and in vitro. B. An integrative approach to the endocrinology of ageing. Hormonal factors related to the ageing process are investigated in population studies. Intervention studies with hormones (growth hormone, dehydroepiandrosterone) are carried out. C. An integrative approach to factors determining glucocorticoid sensitivity in man. Molecular studies of mutations in the glucocorticoid receptor and in the translational regulation of glucocorticoid action are carried out in cells obtained from patients with glucocorticoid resistance and from patients with transient changes in glucocorticoid sensitivity. D. Studies on the expression of growth factor and peptide receptors in cancer and in immune cells. E. The regulation of the growth and activity of immune and of tumour cells in vitro by manipulation of the expression of peptide receptors is studied in relation with the potential endocrine manipulation of immune diseases and cancer growth in vivo. F. An integrative approach of clinical and surgical endocrinology is used in studies aimed at improving patient care. Key figures Department SP1 SP2 SP3 SP4 Sptot T1 T2 T3 Ttot IS FS OP Ptot internal medicine 1,9 1,4 0,82 3,67 7,79 surgery 0, ,1 Total 2 1,4 0,82 3,67 7, Thesis Brugts, M.P. (2010, januari 06). IGF-I bioactivity in aging, health and disease. EUR (252 pag.). Prom./coprom.: Prof.Dr. S.W.J. Lamberts & Dr. J.A.M.J.L. Janssen. Artikel/Letter to the editor Alwani, R.A., Herder, W.W. de, Aken, M.O. van, Berge, J.H. van den, Delwel, E.J., Dallenga, A.H.G., Jong, F.H. de, Lamberts, S.W.J, Lelij, A.J. van der & Feelders, R.A. (2010). Biochemical Predictors of Outcome of Pituitary Surgery for Cushing's Disease. Neuroendocrinology, 91(2), Brugts, M.P., Tjiong, H.L., Rietveld, T., Wattimena, J.L.D., Berg, J.W.O. van den, Fieren, M.W.J.A. & Janssen, J.A.M.J.L. (2010). Bioactive rather than total IGF-I is involved in acute responses to nutritional interventions in CAPD patients. Nephrology Dialysis Transplantation, 25(3), Brugts, M.P., Duijn, C.M. van, Hofland, L.J., Witteman, J.C.M., Lamberts, S.W.J & Janssen, J.A.M.J.L. (2010). IGF-I Bioactivity in an Elderly Population Relation to Insulin Sensitivity, Insulin Levels, and the Metabolic Syndrome. Diabetes, 59(2), Bruynzeel, J.A., Feelders, R.A., Groenland, T.H.N., Meiracker, A.H. van den, Eijck, C.H.J. van, Lange, J.F., Herder, W.W. de & Kazemier, G. (2010). Risk Factors for Hemodynamic Instability during Surgery for Pheochromocytoma. Journal of Clinical Endocrinology and Metabolism, 95(2), Chai, W., Hofland, J., Jansen, P.M., Garrelds, I.M., Vries, R.D. de, Bogaerdt, A.J. van den, Feelders, R.A., Jong, F.H. de & Danser, A.H.J. (2010). Steroidogenesis vs. steroid uptake in the heart: do corticosteroids mediate effects via cardiac mineralocorticoid receptors? Journal of Hypertension, 28(5), Daly, AF, Tichomirowa, MA, Petrossians, P., Heliovaara, E, Jaffrain-Rea, ML, Barlier, A, Naves, LA, Ebeling, T, Karhu, A, Raappana, A, Cazabat, L, Menis, E De, Montanana, CF, Raverot, G, Weil, RJ, Sane, T, Maiter, D, Neggers, S.J.C.M.M., Yaneva, M, Tabarin, A, Verrua, E, Eloranta, E, Murat, A, Vierimaa, O, Salmela, PI, Emy, P, Toledo, RA, Sabate, MI, Villa, C, Popelier, M, Salvatori, R, Jennings, J, Longas, AF, Aizpun, JIL, Georgitsi, M., Paschke, R, Ronchi, C, Valimaki, M, Saloranta, C, Herder, W.W. de, Cozzi, R, Guitelman, M, Magri, F, Lagonigro, MS, Halaby, G, Corman, V, Hagelstein, MT, Vanbellinghen, JF, Barra, GB, Gimenez-Roqueplo, AP, Cameron, FJ, Borson-Chazot, F, Holdaway, I, Toledo, S.P.A., Stalla, GK, Spada, A, Zacharieva, S, Bertherat, J, Brue, T, Bours, V, Chanson, P., Aaltonen, LA & Beckers, A. (2010). Clinical Characteristics and Therapeutic Responses in Patients with Germ-Line AIP Mutations and Pituitary Adenomas: An International Collaborative Study. Journal of Clinical Endocrinology and Metabolism, 95(11), E373-E383. Delhanty, P.J.D., Sun, YX, Visser, J.A., Kerkwijk, A.J. van, Huisman, M., Ijcken, W.F.J. van, Swagemakers, S.M.A., Smith, RG, Themmen, A.P.N. & Lelij, A.J. van der (2010). Unacylated Ghrelin Rapidly Modulates Lipogenic and Insulin Signaling Pathway Gene Expression in Metabolically Active Tissues of GHSR Deleted Mice. PLoS One, 5(7). Delhanty, P.J.D., Kerkwijk, A.J. van, Huisman, M., Zande, B. van de, Verhoef-Post, M., Gauna, C., Hofland, L.J., Themmen, A.P.N. & Lelij, A.J. van der (2010). Unsaturated fatty acids prevent desensitization of the human growth hormone secretagogue receptor by blocking its internalization. American Journal of Physiology, Endocrinology and Metabolism, 299(3), E497-E505. Essen, M. van, Krenning, E.P., Kam, B.L.R., Herder, W.W. de, Feelders, R.A. & Kwekkeboom, D.J. (2010). Salvage Therapy with Lu-177-Octreotate in Patients with Bronchial and Gastroenteropancreatic Neuroendocrine Tumors. Journal of Nuclear Medicine, 51(3), Feelders, R.A., Hofland, L.J. & Herder, W.W. de (2010). Medical Treatment of Cushing's Syndrome: Adrenal-Blocking Drugs and Ketaconazole. Neuroendocrinology, 92,

7 Feelders, R.A., Bruin, C. de, Pereira, AM, Romijn, J.A., Netea-Maier, RT, Hermus, A.R., Zelissen, PM, Heerebeek, R.E.A. van, Jong, F.H. de, Lelij, A.J. van der, Herder, W.W. de, Hofland, L.J. & Lamberts, S.W.J (2010). Pasireotide Alone or with Cabergoline and Ketoconazole in Cushing's Disease. New England Journal of Medicine, 362(19), Giustina, A, Chanson, P., Bronstein, MD, Klibanski, A., Lamberts, S.W.J, Casanueva, F.F., Trainer, P, Ghigo, E., Ho, K & Melmed, S. (2010). A Consensus on Criteria for Cure of Acromegaly. Journal of Clinical Endocrinology and Metabolism, 95(7), Granata, R, Volante, M., Settanni, F, Gauna, C., Ghe, C, Annunziata, M, Deidda, B, Gesmundo, I, Abribat, T., Lelij, A.J. van der, Muccioli, G., Ghigo, E. & Papotti, M. (2010). Unacylated ghrelin and obestatin increase islet cell mass and prevent diabetes in streptozotocin-treated newborn rats. Journal of Molecular Endocrinology, 45(1), Groot, JWB de, Links, T.P., Themmen, A.P.N., Looijenga, L.H.J., Krijger, R.R. de, Koetsveld, P.M. van, Hofland, J., Berg, G. van den, Hofland, L.J. & Feelders, R.A. (2010). Aberrant expression of multiple hormone receptors in ACTH-independent macronodular adrenal hyperplasia causing Cushing's syndrome. European Journal of Endocrinology, 163(2), Hoek, J. van der, Lamberts, S.W.J & Hofland, L.J. (2010). The somatostatin receptor subtype 5 in neuroendocrine tumours. Expert Opinion on Investigational Drugs, 19(3), Hofland, L.J., Feelders, R.A., Herder, W.W. de & Lamberts, S.W.J (2010). Pituitary tumours: The sst/d-2 receptors as molecular targets. Molecular and Cellular Endocrinology, 326(1-2), Hofland, L.J., Lamberts, S.W.J & Feelders, R.A. (2010). Role of Somatostatin Receptors in Normal and Tumoral Pituitary Corticotropic Cells. Neuroendocrinology, 92, Kaltsas, G., Androulakis, II, Herder, W.W. de & Grossman, A.B. (2010). Paraneoplastic syndromes secondary to neuroendocrine tumours. Endocrine-Related Cancer, 17(3), R173-R193. Kianmanesh, R., Ruszniewski, P., Rindi, G., Kwekkeboom, D.J., Pape, U.F., Kulke, M, Garcia, IS, Scoazec, JY, Nilsson, O., Fazio, N, Lesurtel, M, Chen, YJ, Eriksson, B., Cioppi, F & O'Toole, D (2010). ENETS Consensus Guidelines for the Management of Peritoneal Carcinomatosis from Neuroendocrine Tumors. Neuroendocrinology, 91(4), Kulke, MH, Anthony, LB, Bushnell, DL, Herder, W.W. de, Goldsmith, S.J., Klimstra, D.S., Marx, SJ, Pasieka, JL, Pommier, RF, Yao, J.C. & Jensen, R.T. (2010). NANETS Treatment Guidelines Well-Differentiated Neuroendocrine Tumors of the Stomach and Pancreas. Pancreas, 39(6), Kumsta, R., Entringer, S, Koper, J.W., Rossum, E.F.C. van, Hellhammer, D.H. & Wust, S (2010). Working memory performance is associated with common glucocorticoid receptor gene polymorphisms. Neuropsychobiology, Kwekkeboom, D.J., Herder, W.W. de, Eijck, C.H.J. van, Kam, B.L.R., Essen, M. van, Teunissen, J.J.M. & Krenning, E.P. (2010). Peptide Receptor Radionuclide Therapy in Patients With Gastroenteropancreatic Neuroendocrine Tumors. Seminars in Nuclear Medicine, 40(2), Kwekkeboom, D.J., Kam, B.L.R., Essen, M. van, Teunissen, J.J.M., Eijck, C.H.J. van, Valkema, R., Jong, M. de, Herder, W.W. de & Krenning, E.P. (2010). Somatostatin receptor-based imaging and therapy of gastroenteropancreatic neuroendocrine tumors. Endocrine-Related Cancer, 17(1), R53-R73. Lelij, A.J. van der (2010). Multiple Sources of Information for the Hypothalamus. Frontiers of Hormone Research, 38, Manenschijn, L., Akker, E.L.T. van den, Ester, W.A., Leunissen, R.W.J., Willemsen, R.H., Rossum, E.F.C. van, Koper, F.J.W., Lamberts, S.W.J & Hokken-Koelega, A.C.S. (2010). Glucocorticoid receptor gene haplotypes are not associated with birth anthropometry, blood pressure, glucose and insulin concentrations, and body composition in subjects born small for gestational age. European Journal of Endocrinology, 163, Martino, M.C. de, Koetsveld, P.M. van, Pivonello, R. & Hofland, L.J. (2010). Role of the mtor Pathway in Normal and Tumoral Adrenal Cells. Neuroendocrinology, 92, Martino, M.C. de, Hofland, L.J. & Lamberts, S.W.J (2010). Somatostatin and somatostatin receptors: from basic concepts to clinical applications. Progress in Brain Research, 182, Oosten, M.J.M. van, Dolhain, R.J.E.M., Koper, F.J.W., Rossum, E.F.C. van, Emonts, M., Han, KH, Wouters, J.M.G.W., Hazes, J.M.W., Lamberts, S.W.J & Feelders, R.A. (2010). Polymorphisms in the glucocorticoid receptor gene that modulate glucocorticoid sensitivity are associated with rheumatoid arthritis. Arthritis Research & Therapy, 12(4). Pavel, M, Grossman, A., Arnold, R., Perren, A, Kaltsas, G., Steinmuller, T., Herder, W.W. de, Nikou, G., Plockinger, U, Lopes, JM, Sasano, H, Buscombe, J, Lind, P, O'Toole, D & Oberg, K (2010). ENETS Consensus Guidelines for the Management of Brain, Cardiac and Ovarian Metastases from Neuroendocrine Tumors. Neuroendocrinology, 91(4), Pereira, AM, Delgado, V, Romijn, J.A., Smit, J.W.A., Bax, J.J. & Feelders, R.A. (2010). Cardiac dysfunction is reversed upon successful treatment of Cushing's syndrome. European Journal of Endocrinology, 162(2), Varewijck, A.J., Goudzwaard, J.A., Brugts, M.P., Lamberts, S.W.J, Hofland, L.J. & Janssen, J.A.M.J.L. (2010). Insulin glargine is more potent in activating the human IGF-I receptor than human insulin and insulin detemir. Growth Hormone and IGF Research, 20(6), Waas, M. van, Neggers, S.J.C.M.M., Pieters, R. & Heuvel-Eibrink, M.M. van den (2010). Components of the metabolic syndrome in 500 adult long-term survivors of childhood cancer. Annals of Oncology, 21,

8 Webb, S.M., Mo, DJ, Lamberts, S.W.J, Melmed, S., Cavagnini, F., Giraldi, FP, Strasburger, C.J., Zimmermann, AG & Woodmansee, WW (2010). Metabolic, Cardiovascular, and Cerebrovascular Outcomes in Growth Hormone-Deficient Subjects with Previous Cushing's Disease or Non-Functioning Pituitary Adenoma. Journal of Clinical Endocrinology and Metabolism, 95(2), Woodmansee, WW, Hartman, M.L., Lamberts, S.W.J, Zagar, AJ & Clemmons, D.R. (2010). Occurrence of impaired fasting glucose in GH-deficient adults receiving GH replacement compared with untreated subjects. Clinical Endocrinology, 72, Part of book - abstract Herder, W.W. de & Feelders, R.A. (2010). Imaging for the Differential Diagnosis of Cushing s Syndrome: MRI, CT and Isotopic Scanning. In M Bronstein (Ed.), Cushings Syndrome Pathophysiology, Diagnosis and Treatment. Contemporary Endocrinology (pp ). New York: Humana Press. Rossum, E.F.C. van & Lamberts, S.W.J (2010). Glucocorticoid Resistance. In M Bronstein (Ed.), Cushing's Syndrome, Pathophysiology, Diagnosis and Treatment (pp ). New York: Humana Press. 74

9 EMC MM Regulation of calcium and bone metabolism Programme in brief design Research focus is skeletal and calcium homeostasis and development and progression of related disorders with particular emphasis on ageing. Increasing life span is accompanied by an increase in age-related diseases such as osteoporosis. Osteoporosis is an important common disease with a large impact on quality of life as well as health care budget. Development of pharmaceutical and life style interventions as prevention or as treatment is important and requires an optimal knowledge in aetiology and mechanisms of development of osteoporosis. Current therapies for osteoporosis are directed to inhibit bone loss and thereby its progression. There is, however, a major need for anabolic therapies which stimulate bone formation because bone loss has already occurred when the consequences of osteoporosis have become overt. Directly coupled to this is improvement in early diagnostics. The overall aim of this research line is to develop better diagnostics and therapies for skeletal disorders and disturbances in calcium homeostasis by a combination of molecular, cellular, animal, epidemiological and eventually clinical studies. Four integrated lines of research can be identified. 1) Characterisation of molecular mechanisms of bone cell differentiation and of bone formation and degradation using human bone cell models by bioinformatic and systems biological analyses of gene, protein and enzyme activity profiles. 2) Identification of risk determinants for osteoporosis and osteoarthritis on basis of genetic epidemiological and serum proteomic studies within a.o. the Rotterdam Study. 3) Calcium homeostasis and skeletal metabolism in relation to ageing by analyses of experimental animal models, e.g. premature ageing mice, as well as human population research. 4) Development of medium/high throughput screenings procedures to quickly screen therapeutic targets and to evaluate novel therapeutic compounds Key figures Department SP1 SP2 SP3 SP4 Sptot T1 T2 T3 Ttot IS FS OP Ptot internal medicine 12,31 3,74 0 2,64 18,69 Total 12,31 3,74 0 2,64 18, Thesis Botter, S.M. (2010, december 21). Dynamic subchondral bone changes in murine models of osteoarthritis. EUR (172 pag.). Prom./coprom.: Prof. Dr. Ir. H.H. Weinans, Prof.dr. J.P.T.M. van Leeuwen & Dr. G.J.V.M. van Osch. Diderich, K.E.M. (2010, januari 06). Bone aging in DNA Repair deficient trichothiodystrophy mice. EUR (252 pag.). Prom./coprom.: Prof. Dr. J.H.J. Hoeijmakers, Prof. Dr. G.T.J. van der Horst & Prof.dr. J.P.T.M. van Leeuwen. Jansen, J.H.W. (2010, mei 12). Mechanotransduction in bone, Dependency on Human Osteoblast Differation. EUR (133 pag.). Prom./coprom.: Prof. Dr. Ir. H.H. Weinans & Prof.dr. J.P.T.M. van Leeuwen. Artikel/Letter to the editor Allen, HL, Estrada, K, Lettre, G., Berndt, SI, Weedon, MN, Rivadeneira Ramirez, F., Willer, CJ, Jackson, AU, Vedantam, S, Raychaudhuri, S, Ferreira, T, Wood, AR, Weyant, RJ, Segre, AV, Speliotes, EK, Wheeler, E, Soranzo, N, Park, JH, Yang, J., Gudbjartsson, D, Heard-Costa, NL, Randall, JC, Qi, L., Smith, AV, Magi, R, Pastinen, T, Liang, L., Heid, IM, Luan, J, Thorleifsson, G, Winkler, TW, Goddard, ME, Lo, KS, Palmer, C, Workalemahu, T, Aulchenko, Y.S., Johansson, A, Zillikens, M.C., Feitosa, MF, Esko, T, Johnson, T, Ketkar, S., Kraft, P, Mangino, M, Prokopenko, I, Absher, D, Albrecht, E, Ernst, F, Glazer, NL, Hayward, C, Hottenga, J.J., Jacobs, KB, Knowles, JW, Kutalik, Z, Monda, KL, Polasek, O, Preuss, M, Rayner, NW, Robertson, NR, Steinthorsdottir, V, Tyrer, JP, Voight, BF, Wiklund, F, Xu, J.F., Zhao, JH, Nyholt, DR, Pellikka, N, Perola, M, Perry, JRB, Surakka, I, Tammesoo, ML, Altmaier, EL, Amin, N., Aspelund, T, Bhangale, T, Boucher, G, Chasman, DI, Chen, C., Coin, L, Cooper, MN, Dixon, AL, Gibson, Q, Grundberg, E, Hao, K, Junttila, MJ, Kaplan, LM, Kettunen, J, Konig, IR, Kwan, T, Lawrence, RW, Levinson, DF, Lorentzon, M, McKnight, B, Morris, AP, Muller, M., Ngwa, JS, Purcell, S, Rafelt, S, Salem, RM, Salvi, E, Sanna, S, Shi, JX, Sovio, U, Thompson, JR, Turchin, MC, Vandenput, L, Verlaan, DJ, Vitart, V, White, CC, Ziegler, A, Almgren, P, Balmforth, AJ, Campbell, H, Citterio, L., Grandi, A De, Dominiczak, A, Duan, J, Elliott, P., Elosua, R, Eriksson, JG, Freimer, N.B., Geus, E.J.C. de, Glorioso, N, Haiqing, S, Hartikainen, AL, Havulinna, AS, Hicks, AA, Hui, JN, Igl, W, Illig, T, Jula, A, Kajantie, E, Kilpelaeinen, TO, Koiranen, M, Kolcic, I, Koskinen, S, Kovacs, P, Laitinen, J, Liu, JJ, Lokki, ML, Marusic, A, Maschio, A. del, Meitinger, T, Mulas, A, Pare, G, Parker, AN, Peden, JF, Petersmann, A, Pichler, I, Pietilainen, KH, Pouta, A, Riddertrale, M, Rotter, JI, Sambrook, JG, Sanders, AR, Schmidt, CO, Sinisalo, J, Smit, J.H., Stringham, HM, Walters, GB, Widen, E, Wild, SH, Willemsen, G, Zagato, L, Zgaga, L, Zitting, P, Alavere, H, Farrall, M, McArdle, WL, Nelis, M, Peters, M.J., Ripatti, S, Meurs, J.B.J. van, Aben, KK, Ardlie, KG, Beckmann, J.S., Beilby, JP, Bergman, RN, Bergmann, S, Collins, FS, Cusi, D, Heijer, M. den, Eiriksdottir, G, Gejman, PV, Hall, AS, Hamsten, A., Huikuri, HV, Iribarren, C, Kahonen, M, Kaprio, J, Kathiresan, S, Kiemeney, L, Kocher, T, Launer, L.J., Lehtimaki, T, Melander, O, Mosley, TH, Musk, AW, Nieminen, MS, O'Donnell, CJ, Ohlsson, C, Oostra, B.A., Palmer, LJ, Raitakari, O, Ridker, P.M., Rioux, JD, Rissanen, A, Rivolta, C, Schunkert, H., Shuldiner, AR, Siscovick, D.S., Stumvoll, M., Tonjes, A, Tuomilehto, J, Ommen, G.J. van, Viikari, J, Heath, AC, Martin, NG, Montgomery, GW, Province, MA, Kayser, M., Arnold, AM, Atwood, LD, Boerwinkle, E., Chanock, SJ, Deloukas, P, Gieger, C, Gronberg, H, Hall, P., Hattersley, A.T., Hengstenberg, C, Hoffman, W, Lathrop, GM, Salomaa, V, Schreiber, S., Uda, M, Waterworth, D, Wright, AF, Assimes, TL, Barroso, I, Hofman, A., Mohlke, KL, Boomsma, D.I., Caulfield, MJ, Cupples, L.A., Erdmann, J., Fox, CS, Gudnason, V, Gyllensten, U, Harris, T.B., Hayes, RB, Jarvelin, MR, Mooser, V, Munroe, PB, Ouwehand, WH, Penninx, BW, Pramstaller, P.P., Quertermous, T, Rudan, I, Samani, NJ, Spector, T.D., Volzke, H, Watkins, H, Wilson, JF, Groop, LC, Haritunians, T, Hu, FB, Kaplan, RC, Metspalu, A, North, KE, Schlessinger, D, Wareham, NJ, Hunter, DJ, O'Connell, JR, Strachan, DP, Schadt, HE, Thorsteinsdottir, U, Peltonen, L., Uitterlinden, A.G., Visscher, P.M., Chatterjee, N, Loos, RJF, Boehnke, M, McCarthy, MI, Ingelsson, E, Lindgren, CM, Abecasis, GR, Stefansson, K, Frayling, T.M. & Hirschhorn, JN (2010). Hundreds of variants clustered in genomic loci and biological pathways affect human height. Nature, 467(7317),

10 Alves, R., Eijken, M, Swagemakers, S.M.A., Chiba, H., Titulaer, M.K., Burgers, P.C., Luider, T.M. & Leeuwen, J.P.T.M. van (2010). Proteomic Analysis of Human Osteoblastic Cells: Relevant Proteins and Functional Categories for Differentiation. Journal of Proteome Research, 9(9), Anttila, V, Stefansson, H, Kallela, M, Todt, U, Terwindt, G.M., Calafato, MS, Nyholt, DR, Dimas, AS, Freilinger, T, Muller- Myhsok, B, Artto, V, Inouye, M, Alakurtti, K, Kaunisto, MA, Hamalainen, E, Vries, B de, Stam, AH, Weller, CM, Heinze, A, Heinze-Kuhn, K, Goebel, I, Borck, G, Gobel, H, Steinberg, S, Wolf, C, Bjornsson, A, Gudmundsson, G, Kirchmann, M, Hauge, A, Werge, T, Schoenen, J., Eriksson, JG, Hagen, K, Stovner, L, Wichmann, E, Meitinger, T, Alexander, M, Moebus, S, Schreiber, S., Aulchenko, Y.S., Breteler, M.M.B., Uitterlinden, A.G., Hofman, A., Duijn, C.M. van, Tikka-Kleemola, P, Vepsalainen,., Lucae, S, Tozzi, F, Muglia, P, Barrett, J, Kaprio, J, Farkkila, M, Peltonen, L., Stefansson, K, Zwart, JA, Ferrari, M.D., Olesen, J, Daly, M., Wessman, M, Maagdenberg, A.M.J.M., Dichgans, M, Kubisch, C, Dermitzakis, ET, Frants, R.R. & Palotie, A (2010). Genome-wide association study of migraine implicates a common susceptibility variant on 8q22.1. Nature Genetics, 42(10), Baas, DC, Ho, L., Ennis, S, Merriam, JE, Tanck, M.W.T., Uitterlinden, A.G., Jong, P.T.V.M. de, Cree, AJ, Griffiths, HL, Rivadeneira, F., Hofman, A., Duijn, C.M. van, Smith, R.T., Barile, GR, Gorgels, TGMF, Vingerling, J.R., Klaver, C.C.W., Lotery, AJ, Allikmets, R. & Bergen, A.A.B. (2010). The Complement Component 5 Gene and Age-Related Macular Degeneration. Ophthalmology, 117(3), Baas, DC, Despriet, D.D., Gorgels, T.G.M.F., Bergeron-Sawitzke, J, Uitterlinden, A.G., Hofman, A., Duijn, C.M. van, Merriam, JE, Smith, R.T., Barile, GR, Brink, J.B., Vingerling, J.R., Klaver, C.C.W., Allikmets, R., Dean, M & Bergen, A.A.B. (2010). The ERCC6 Gene and Age-Related Macular Degeneration. PLoS One, 5(11). Barbalic, M, Dupuis, J, Dehghan, A., Bis, JC, Hoogeveen, RC, Schnabel, RB, Nambi, V, Bretler, M, Smith, NL, Peters, A., Lu, C, Tracy, RP, Aleksic, N, Heeriga, J, Keaney, JF, Rice, K, Lip, G.Y.H., Vasan, RS, Glazer, NL, Larson, MG, Uitterlinden, A.G., Yamamoto, J, Durda, P, Haritunians, T, Psaty, B.M., Boerwinkle, E., Hofman, A., Koenig, W., Jenny, NS, Witteman, J.C.M., Ballantyne, C. & Benjamin, EJ (2010). Large-scale genomic studies reveal central role of ABO in sp-selectin and sicam-1 levels. Human Molecular Genetics, 19(9), Becker, M.L., Visser, L.E., Schaik, R.H.N. van, Hofman, A., Uitterlinden, A.G. & Stricker, B.H.C. (2010). Interaction between polymorphisms in the OCT1 and MATE1 transporter and metformin response. Pharmacogenetics Genomics, 20(1), Blauw, HM, Al-Chalabi, A, Andersen, PM, Vught, PWJ Van, Diekstra, FP, Es, MA van, Saris, CGJ, Groen, EJN, Rheenen, W van, Koppers, M, Slot, R van 't, Strengman, E., Estrada, K, Rivadeneira, F., Hofman, A., Uitterlinden, A.G., Kiemeney, LA, Vermeulen, SHM, Birve, A, Waibel, S, Meyer, T, Cronin, S, McLaughlin, RL, Hardiman, O, Sapp, PC, Tobin, MD, Wain, LV, Tomik, B, Slowik, A, Lemmens, R, Rujescu, D, Schulte, C, Gasser, T., Brown, RH, Landers, JE, Robberecht, W, Ludolph, A.C., Ophoff, R.A., Veldink, J.H. & Berg, L.H. van den (2010). A large genome scan for rare CNVs in amyotrophic lateral sclerosis. Human Molecular Genetics, 19(20), Bruedigam, C., Eijken, M, Koedam, M., Peppel, J van de, Drabek, K., Chiba, H. & Leeuwen, J.P.T.M. van (2010). A New Concept Underlying Stem Cell Lineage Skewing That Explains the Detrimental Effects of Thiazolidinediones on Bone. Stem Cells, 28(5), Brugts, J.J., Isaacs, A.J., Boersma, E., Duijn, C.M. van, Uitterlinden, A.G., Remme, W, Bertrand, M, Ninomiya, T, Ceconi, C., Chalmers, J, MacMahon, S, Fox, K, Ferrari, R., Witteman, J.C.M., Danser, A.H.J., Simoons, M.L. & Maat, M.P.M. de (2010). Genetic determinants of treatment benefit of the angiotensin-converting enzyme-inhibitor perindopril in patients with stable coronary artery disease. European Heart Journal, 31(15), Colin, E.M., Asmawidjaja, P.S., Hamburg, J.P. van, Mus, A.M.C., Driel, M. van, Hazes, J.M.W., Leeuwen, J.P.T.M. van & Lubberts, E. (2010). 1,25-Dihydroxyvitamin D-3 Modulates Th17 Polarization and Interleukin-22 Expression by Memory T Cells From Patients With Early Rheumatoid Arthritis. Arthritis & Rheumatism, 62(1), Debette, S, Bis, JC, Fornage, M, Schmidt, H., Ikram, M.A., Sigurdsson, S, Heiss, G, Struchalin, M, Smith, AV, Lugt, A. van der, DeCarli, C., Lumley, T, Knopman, DS, Enzinger, C, Eiriksdottir, G, Koudstaal, P.J., DeStefano, AL, Psaty, B.M., Dufouil, C., Catellier, DJ, Fazekas, F., Aspelund, T, Aulchenko, Y.S., Beiser, A, Rotter, JI, Tzourio, C., Shibata, DK, Tscherner, M, Harris, T.B., Rivadeneira, F., Atwood, LD, Rice, K, Gottesman, RF, Buchem, M.A. van, Uitterlinden, A.G., Kelly-Hayes, M, Cushman, M., Zhu, YC, Boerwinkle, E., Gudnason, V, Hofman, A., Romero, JR, Lopez, O, Duijn, C.M. van, Au, R., Heckbert, SR, Wolf, PA, Mosley, TH, Seshadri, S, Breteler, M.M.B., Schmidt, R., Launer, L.J. & Longstreth, W.T. (2010). Genome-Wide Association Studies of MRI-Defined Brain Infarcts Meta-Analysis From the CHARGE Consortium. Stroke, 41(2), Dupuis, J, Langenberg, C, Prokopenko, I, Saxena, R., Soranzo, N, Jackson, AU, Wheeler, E, Glazer, NL, Bouatia-Naji, N, Gloyn, AL, Lindgren, CM, Magi, R, Morris, AP, Randall, J, Johnson, T, Elliott, P., Rybin, D, Thorleifsson, G, Steinthorsdottir, V, Henneman, P., Grallert, H, Dehghan, A., Hottenga, J.J., Franklin, CS, Navarro, P, Song, K, Goel, A, Perry, JRB, Egan, JM, Lajunen, T, Grarup, N, Sparso, T, Doney, A, Voight, BF, Stringham, HM, Li, M., Kanoni, S, Shrader, P, Cavalcanti-Proenca, C, Kumari, M, Qi, L., Timpson, NJ, Gieger, C, Zabena, C, Rocheleau, G, Ingelsson, E, An, P, O'Connell, J, Luan, J, Elliott, A, McCarroll, SA, Payne, F, Roccasecca, RM, Pattou, F, Sethupathy, P, Ardlie, K, Ariyurek, Y., Balkau, B, Barter, P., Beilby, JP, Ben-Shlomo, Y, Benediktsson, R, Bennett, AJ, Bergmann, S, Bochud, M, Boerwinkle, E., Bonnefond, A, Bonnycastle, LL, Borch-Johnsen, K, Bottcher, Y, Brunner, E, Bumpstead, SJ, Charpentier, G, Chen, YDI, Chines, P, Clarke, R., Coin, LJM, Cooper, MN, Cornelis, M, Crawford, G, Crisponi, L, Day, INM, Geus, E.J.C. de, Delplanque, J, Dina, C, Erdos, MR, Fedson, AC, Fischer-Rosinsky, A, Forouhi, NG, Fox, CS, Frants, R, Franzosi, MG, Galan, P, Goodarzi, MO, Graessler, J, Groves, CJ, Grundy, S, Gwilliam, R, Gyllensten, U, Hadjadj, S, Hallmans, G, Hammond, N, Han, XJ, Hartikainen, AL, Hassanali, N, Hayward, C, Heath, SC, Hercberg, S, Herder, C. den, Hicks, AA, Hillman, DR, Hingorani, AD, Hofman, A., Hui, J, Hung, J, Isomaa, B, Johnson, PRV, Jorgensen, T, Jula, A, Kaakinen, M, Kaprio, J, Kesaniemi, YA, Kivimaki, M, Knight, B, Koskinen, S, Kovacs, P, Kyvik, KO, Lathrop, GM, Lawlor, DA, Bacquer, O Le, Lecoeur, C, Li, Y., Lyssenko, V, Mahley, R, Mangino, M, Manning, AK, Martinez-Larrad, MT, McAteer, JB, McCulloch, LJ, McPherson, R, Meisinger, C, Melzer, D, Meyre, D, Mitchell, B.D., Morken, MA, Mukherjee, S., Naitza, S, Narisu, N, Neville, MJ, Oostra, B.A., Orru, M, Pakyz, R, Palmer, CNA, Paolisso, G, 76

11 Pattaro, C, Pearson, D, Peden, JF, Pedersen, NL, Perola, M, Pfeiffer, AFH, Pichler, I, Polasek, O, Posthuma, D, Potter, SC, Pouta, A, Province, MA, Psaty, B.M., Rathmann, W, Rayner, NW, Rice, K, Ripatti, S, Rivadeneira Ramirez, F., Roden, M, Rolandsson, O, Sandbaek, A, Sandhu, M, Sanna, S, Sayer, AA, Scheet, P, Scott, LJ, Seedorf, U, Sharp, SJ, Shields, B, Sigurosson, G, Sijbrands, E.J.G., Silveira, A, Simpson, L, Singleton, A., Smith, NL, Sovio, U, Swift, A., Syddall, H, Syvanen, AC, Tanaka, T, Thorand, B, Tichet, J, Tonjes, A, Tuomi, T, Uitterlinden, A.G., Dijk, KW van, Hoek, M. van, Varma, D, Visvikis-Siest, S, Vitart, V, Vogelzangs, N, Waeber, G, Wagner, PJ, Walley, A, Walters, GB, Ward, KL, Watkins, H, Weedon, MN, Wild, SH, Willemsen, G, Witteman, J.C.M., Yarnell, JWG, Zeggini, E, Zelenika, D, Zethelius, B, Zhai, GJ, Zhao, JH, Zillikens, M.C., Borecki, IB, Loos, RJF, Meneton, P, Magnusson, PKE, Nathan, DM, Williams, GH, Hattersley, A.T., Silander, K, Salomaa, V, Smith, G.D., Bornstein, S.R., Schwarz, P, Spranger, J., Karpe, F, Shuldiner, AR, Cooper, C., Dedoussis, GV, Serrano-Rios, M, Morris, A.D., Lind, L, Palmer, LJ, Hu, FB, Franks, PW, Ebrahim, S, Marmot, M, Kao, WHL, Pankow, JS, Sampson, MJ, Kuusisto, J, Laakso, M., Hansen, T., Pedersen, O, Pramstaller, P.P., Wichmann, HE, Illig, T, Rudan, I, Wright, AF, Stumvoll, M., Campbell, H, Wilson, JF, Bergman, RN, Buchanan, TA, Collins, FS, Mohlke, KL, Tuomilehto, J, Valle, TT, Altshuler, D, Rotter, JI, Siscovick, D.S., Penninx, BWJH, Boomsma, D.I., Deloukas, P, Spector, T.D., Frayling, T.M., Ferrucci, L, Kong, A, Thorsteinsdottir, U, Stefansson, K, Duijn, C.M. van, Aulchenko, Y.S., Cao, A., Scuteri, A, Schlessinger, D, Uda, M, Ruokonen, A, Jarvelin, MR, Waterworth, D.M., Vollenweider, P, Peltonen, L., Mooser, V, Abecasis, GR, Wareham, NJ, Sladek, R, Froguel, P, Watanabe, RM, Meigs, JB, Groop, L, Boehnke, M, McCarthy, MI, Florez, JC & Barroso, I (2010). New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk. Nature Genetics, 42(2), 105-U32. Durme, Y.M.T.A. van, Eijgelsheim, M., Joos, G.F., Hofman, A., Uitterlinden, A.G., Brusselle, GG & Stricker, B.H.C. (2010). Hedgehog-interacting protein is a COPD susceptibility gene: the Rotterdam Study. European Respiratory Journal, 36(1), Eijgelsheim, M., Newton-Cheh, C, Sotoodehnia, N, Bakker, PIW de, Muller, M., Morrison, AC, Smith, AV, Isaacs, A.J., Sanna, S, Dorr, M, Navarro, P, Fuchsberger, C, Nolte, I.M., Geus, E.J.C. de, Estrada, K, Hwang, SJ, Bis, JC, Ruckert, IM, Alonso, A., Launer, L.J., Hottenga, J.J., Rivadeneira Ramirez, F., Noseworthy, PA, Rice, KM, Perz, S, Arking, DE, Spector, T.D., Kors, J.A., Aulchenko, Y.S., Tarasov, KV, Homuth, G., Wild, SH, Marroni, F, Gieger, C, Licht, CM, Prineas, RJ, Hofman, A., Rotter, JI, Hicks, AA, Ernst, F, Najjar, SS, Wright, AF, Peters, A., Fox, ER, Oostra, B.A., Kroemer, HK, Couper, D, Volzke, H, Campbell, H, Meitinger, T, Uda, M, Witteman, J.C.M., Psaty, B.M., Wichmann, HE, Harris, T.B., Kaab, S, Siscovick, D.S., Jamshidi, Y, Uitterlinden, A.G., Folsom, A.R., Larson, MG, Wilson, JF, Penninx, BW, Snieder, H, Pramstaller, P.P., Duijn, C.M. van, Lakatta, EG, Felix, SB, Gudnason, V, Pfeufer, A, Heckbert, SR, Stricker, B.H.C., Boerwinkle, E. & O'Donnell, CJ (2010). Genome-wide association analysis identifies multiple loci related to resting heart rate. Human Molecular Genetics, 19(19), Elks, CE, Perry, JRB, Sulem, P, Chasman, DI, Franceschini, N, He, CY, Lunetta, KL, Visser, J.A., Byrne, EM, Cousminer, DL, Gudbjartsson, DF, Esko, T, Feenstra, B., Hottenga, J.J., Koller, DL, Kutalik, Z, Lin, P, Mangino, M, Marongiu, M, McArdle, PF, Smith, AV, Stolk, L., Wingerden, S.H. van, Zhao, JH, Albrecht, E, Corre, T, Ingelsson, E, Hayward, C, Magnusson, PKE, Smith, EN, Ulivi, S, Warrington, NM, Zgaga, L, Alavere, H, Amin, N., Aspelund, T, Bandinelli, S, Barroso, I, Berenson, GS, Bergmann, S, Blackburn, H, Boerwinkle, E., Buring, JE, Busonero, F, Campbell, H, Chanock, SJ, Chen, W., Cornelis, MC, Couper, D, Coviello, AD, d'adamo, P, Faire, U de, Geus, E.J.C. de, Deloukas, P, Doring, A, Smith, G.D., Easton, D.F., Eiriksdottir, G, Emilsson, V, Eriksson, J, Ferrucci, L, Folsom, A.R., Foroud, T., Garcia, M, Gasparini, P, Geller, F, Gieger, C, Gudnason, V, Hall, P., Hankinson, SE, Ferreli, L, Heath, AC, Hernandez, DG, Hofman, A., Hu, FB, Illig, T, Jarvelin, MR, Johnson, AD, karasik, D., Khaw, KT, Kiel, DP, Kilpelainen, TO, Kolcic, I, Kraft, P, Launer, L.J., Laven, J.S.E., Li, SX, Liu, JJ, Levy, D., Martin, NG, McArdle, WL, Melbye, M, Mooser, V, Murray, JC, Murray, SS, Nalls, MA, Navarro, P, Nelis, M, Ness, AR, Northstone, K, Oostra, B.A., Peacock, M., Palmer, LJ, Palotie, A, Pare, G, Parker, AN, Pedersen, NL, Peltonen, L., Pennell, CE, Pharoah, P., Polasek, O, Plump, AS, Pouta, A, Porcu, E, Rafnar, T, Rice, JP, Ring, SM, Rivadeneira Ramirez, F., Rudan, I, Sala, C, Salomaa, V, Sanna, S, Schlessinger, D, Schork, NJ, Scuteri, A, Segre, AV, Shuldiner, AR, Soranzo, N, Sovio, U, Srinivasan, SR, Strachan, DP, Tammesoo, ML, Tikkanen, E, Toniolo, D., Tsui, K, Tryggvadottir, L, Tyrer, J, Uda, M, Dam, RM van, Meurs, J.B.J. van, Vollenweider, P, Waeber, G, Wareham, NJ, Waterworth, D.M., Weedon, MN, Wichmann, HE, Willemsen, G, Wilson, JF, Wright, AF, Young, L, Zhai, GJ, Zhuang, WV, Bierut, LJ, Boomsma, D.I., Boyd, HA, Crisponi, L, Demerath, EW, Duijn, C.M. van, Econs, M.J., Harris, T.B., Hunter, DJ, Loos, RJF, Metspalu, A, Montgomery, GW, Ridker, P.M., Spector, T.D., Streeten, EA, Stefansson, K, Thorsteinsdottir, U, Uitterlinden, A.G., Widen, E, Murabito, JM, Ong, KK & Murray, A (2010). Thirty new loci for age at menarche identified by a meta-analysis of genome-wide association studies. Nature Genetics, 42(12), 1077-U73. Ellinor, PT, Lunetta, KL, Glazer, NL, Pfeufer, A, Alonso, A., Chung, MK, Sinner, MF, Bakker, PIW de, Mueller, M, Lubitz, SA, Fox, E, Darbar, D, Smith, NL, Smith, JD, Schnabel, RB, Soliman, EZ, Rice, KM, Wagoner, DR Van, Beckmann, BM, Noord, C. van, Wang, K, Ehret, GB, Rotter, JI, Hazen, SL, Steinbeck, G, Smith, AV, Launer, L.J., Harris, T.B., Makino, S, Nelis, M, Milan, DJ, Perz, S, Esko, T, Kottgen, A, Moebus, S, Newton-Cheh, C, Li, M., Moehlenkamp, S, Wang, T.J., Kao, WHL, Vasan, RS, Nothen, MM, MacRae, CA, Stricker, B.H.C., Hofman, A., Uitterlinden, A.G., Levy, D., Boerwinkle, E., Metspalu, A, Topol, E.J., Chakravarti, A, Gudnason, V, Psaty, B.M., Roden, DM, Meitinger, T, Wichmann, HE, Witteman, J.C.M., Barnard, J, Arking, DE, Benjamin, EJ, Heckbert, SR & Kaab, S (2010). Common variants in KCNN3 are associated with lone atrial fibrillation. Nature Genetics, 42(3), 240-U36. Freathy, RM, Mook-Kanamori, D.O., Sovio, U, Prokopenko, I, Timpson, NJ, Berry, DJ, Warrington, NM, Widen, E, Hottenga, J.J., Kaakinen, M, Lange, LA, Bradfield, JP, Kerkhof, M., Marsh, JA, Magi, R, Chen, C.M., Lyon, HN, Kirin, M, Adair, LS, Aulchenko, Y.S., Bennett, AJ, Borja, JB, Bouatia-Naji, N, Charoen, P, Coin, LJM, Cousminer, DL, Geus, E.J.C. de, Deloukas, P, Elliott, P, Evans, DM, Froguel, P, Glaser, B., Groves, CJ, Hartikainen, AL, Hassanali, N, Hirschhorn, JN, Hofman, A., Holly, J.M.P., Hypponen, E, Kanoni, S, Knight, BA, Laitinen, J, Lindgren, CM, McArdle, WL, O'Reilly, PF, Pennell, CE, Postma, D.S., Pouta, A, Ramasamy, A, Rayner, NW, Ring, SM, Rivadeneira, F., Shields, BM, Strachan, DP, Surakka, I, Taanila, A, Tiesler, C, Uitterlinden, A.G., Duijn, C.M. van, Wijga, A.H., Willemsen, G, Zhang, HT, Zhao, JH, Wilson, JF, Steegers, E.A.P., Hattersley, A.T., Eriksson, JG, Peltonen, L., Mohlke, KL, Grant, S.F.A., Hakonarson, H, Koppelman, G.H., Dedoussis, GV, Heinrich, J., Gillman, MW, Palmer, LJ, Frayling, T.M., Boomsma, D.I., Smith, G.D., Power, C, Jaddoe, V.W.V.K., Jarvelin, MR & McCarthy, MI (2010). Variants in ADCY5 and near CCNL1 are associated with fetal growth and birth weight. Nature Genetics, 42(5), 430- U73. Gelok, S., Janssens, A.C.J.W., Tiemeier, H.W., Liu, F., Lopez-Leon, S, Zorkoltseva, IV, Axenovich, T.I., Swieten, J.C. van, Uitterlinden, A.G., Hofman, A., Aulchenko, Y.S., Oostra, B.A. & Duijn, C.M. van (2010). A Genome-Wide Screen for Depression in Two Independent Dutch Populations. Biological Psychiatry, 68(2),

12 Graaff, L.C.G. de, Argente, J., Meurs, J.B.J. van, Uitterlinden, A.G. & Hokken-Koelega, A.C.S. (2010). Genetic polymorphisms in the locus control region and promoter of GH1 are related to serum IGF-I levels and height in patients with isolated growth hormone deficiency and healthy controls. Hormone Research, 73, Graaff, L.C.G. de, Argente, J., Veenma, D.C.M., Drent, M., Uitterlinden, A.G. & Hokken-Koelega, A.C.S. (2010). PROP1, HESX1, POU1F1. LHX3 and LHX4 mutation and deletion screening and GH1 P89L and IVS3+1/+2 mutation screening in a Dutch nationwide cohort of patients with combined pituitary hormone deficiency. Hormone Research, 73, Hancock, DB, Eijgelsheim, M., Wilk, JB, Gharib, SA, Loehr, LR, Marciante, KD, Franceschini, N, Durme, Y.M.T.A. van, Chen, TH, Barr, RG, Schabath, MB, Couper, DJ, Brusselle, GG, Psaty, B.M., Duijn, C.M. van, Rotter, JI, Uitterlinden, A.G., Hofman, A., Punjabi, NM, Rivadeneira Ramirez, F., Morrison, AC, Enright, P.L., North, KE, Heckbert, SR, Lumley, T, Stricker, B.H.C., O'Connor, GT & London, SJ (2010). Meta-analyses of genome-wide association studies identify multiple loci associated with pulmonary function. Nature Genetics, 42(1), 45-U61. Heid, IM, Jackson, AU, Randall, JC, Winkler, TW, Qi, L., Steinthorsdottir, V, Thorleifsson, G, Zillikens, M.C., Speliotes, EK, Magi, R, Workalemahu, T, White, CC, Bouatia-Naji, N, Harris, T.B., Berndt, SI, Ingelsson, E, Willer, CJ, Weedon, MN, Luan, JA, Vedantam, S, Esko, T, Kilpelainen, TO, Kutalik, Z, Li, SX, Monda, KL, Dixon, AL, Holmes, CC, Kaplan, LM, Liang, LM, Min, JL, Moffatt, MF, Molony, C, Nicholson, G, Schadt, EE, Zondervan, KT, Feitosa, MF, Ferreira, T, Allen, HL, Weyant, RJ, Wheeler, E, Wood, AR, Estrada, K, Goddard, ME, Lettre, G., Mangino, M, Nyholt, DR, Purcell, S, Smith, AV, Visscher, P.M., Yang, JA, McCarroll, SA, Nemesh, J, Voight, BF, Absher, D, Amin, N., Aspelund, T, Coin, L, Glazer, NL, Hayward, C, Heard-Costa, NL, Hottenga, J.J., Johansson, A, Johnson, T, Kaakinen, M, Kapur, K, Ketkar, S., Knowles, JW, Kraft, P, Kraja, AT, Lamina, C, Leitzmann, MF, McKnight, B, Morris, AP, Ong, KK, Perry, JRB, Peters, M.J., Polasek, O, Prokopenko, I, Rayner, NW, Ripatti, S, Rivadeneira Ramirez, F., Robertson, NR, Sanna, S, Sovio, U, Surakka, I, Teumer, A, Wingerden, S van, Vitart, V, Zhao, JH, Cavalcanti-Proenca, C, Chines, PS, Fisher, E, Kulzer, JR, Lecoeur, C, Narisu, N, Sandholt, C, Scott, LJ, Silander, K, Stark, K, Tammesoo, ML, Teslovich, TM, Timpson, NJ, Watanabe, RM, Welch, R, Chasman, DI, Cooper, MN, Jansson, JO, Kettunen, J, Lawrence, RW, Pellikka, N, Perola, M, Vandenput, L, Alavere, H, Almgren, P, Atwood, LD, Bennett, AJ, Biffar, R, Bonnycastle, LL, Bornstein, S.R., Buchanan, TA, Campbell, H, Day, INM, Dei, M, Dorr, M, Elliott, P., Erdos, MR, Eriksson, JG, Freimer, N.B., Fu, M, Gaget, S, Geus, E.J.C. de, Gjesing, AP, Grallert, H, Grassler, J, Groves, CJ, Guiducci, C, Hartikainen, AL, Hassanali, N, Havulinna, AS, Herzig, KH, Hicks, AA, Hui, JN, Igl, W, Jousilahti, P, Jula, A, Kajantie, E, Kinnunen, L, Kolcic, I, Koskinen, S, Kovacs, P, Kroemer, HK, Krzelj, V, Kuusisto, J, Kvaloy, K, Laitinen, J, Lantieri, O, Lathrop, GM, Lokki, ML, Luben, RN, Ludwig, B., McArdle, WL, McCarthy, A, Morken, MA, Nelis, M, Neville, MJ, Pare, G, Parker, AN, Peden, JF, Pichler, I, Pietilainen, KH, Platou, CGP, Pouta, A, Ridderstrale, M, Samani, NJ, Saramies, J, Sinisalo, J, Smit, J.H., Strawbridge, RJ, Stringham, HM, Swift, AJ, Teder-Laving, M, Thomson, B, Usala, G, Meurs, J.B.J. van, Ommen, G.J. van, Vatin, V, Volpato, CB, Wallaschofski, H., Walters, GB, Widen, E, Wild, SH, Willemsen, G, Witte, DR, Zgaga, L, Zitting, P, Beilby, JP, James, AL, Kahonen, M, Lehtimaki, T, Nieminen, MS, Ohlsson, C, Palmer, LJ, Raitakari, O, Ridker, P.M., Stumvoll, M., Tonjes, A, Viikari, J, Balkau, B, Ben-Shlomo, Y, Bergman, RN, Boeing, H., Smith, G.D., Ebrahim, S, Froguel, P, Hansen, T., Hengstenberg, C, Hveem, K, Isomaa, B, Jorgensen, T, Karpe, F, Khaw, KT, Laakso, M., Lawlor, DA, Marre, M., Meitinger, T, Metspalu, A, Midthjell, K, Pedersen, O, Salomaa, V, Schwarz, PEH, Tuomi, T, Tuomilehto, J, Valle, TT, Wareham, NJ, Arnold, AM, Beckmann, J.S., Bergmann, S, Boerwinkle, E., Boomsma, D.I., Caulfield, MJ, Collins, FS, Eiriksdottir, G, Gudnason, V, Gyllensten, U, Hamsten, A., Hattersley, A.T., Hofman, A., Hu, FB, Illig, T, Iribarren, C, Jarvelin, MR, Kao, WHL, Kaprio, J, Launer, L.J., Munroe, PB, Oostra, B.A., Penninx, BW, Pramstaller, P.P., Psaty, B.M., Quertermous, T, Rissanen, A, Rudan, I, Shuldiner, AR, Soranzo, N, Spector, T.D., Syvanen, AC, Uda, M, Uitterlinden, A.G., Volzke, H, Vollenweider, P, Wilson, JF, Witteman, J.C.M., Wright, AF, Abecasis, GR, Boehnke, M, Borecki, IB, Deloukas, P, Frayling, T.M., Groop, LC, Haritunians, T, Hunter, DJ, Kaplan, RC, North, KE, O'Connell, JR, Peltonen, L., Schlessinger, D, Strachan, DP, Hirschhorn, JN, Assimes, TL, Wichmann, HE, Thorsteinsdottir, U, Duijn, C.M. van, Stefansson, K, Cupples, L.A., Loos, RJF, Barroso, I, McCarthy, MI, Fox, CS, Mohlke, KL & Lindgren, CM (2010). Meta-analysis identifies 13 new loci associated with waist-hip ratio and reveals sexual dimorphism in the genetic basis of fat distribution. Nature Genetics, 42(11), 949-U160. Hek, K., Mulder, C.L., Luijendijk, H.J., Duijn, C.M. van, Hofman, A., Uitterlinden, A.G. & Tiemeier, H.W. (2010). The PCLO gene and depressive disorders: replication in a population-based study. Human Molecular Genetics, 19(4), Hsu, YH, Zillikens, M.C., Wilson, S.G., Farber, CR, Demissie, S, Soranzo, N, Bianchi, EN, Grundberg, E, Liang, LM, Richards, JB, Estrada, K, Zhou, Y., Nas, A van, Moffatt, MF, Zhai, G., Hofman, A., Meurs, J.B.J. van, Pols, H.A.P., Price, RI, Nilsson, O., Pastinen, T, Cupples, L.A., Lusis, AJ, Schadt, EE, Ferrari, S, Uitterlinden, A.G., Rivadeneira Ramirez, F., Spector, T.D., karasik, D. & Kiel, DP (2010). An Integration of Genome-Wide Association Study and Gene Expression Profiling to Prioritize the Discovery of Novel Susceptibility Loci for Osteoporosis-Related Traits. PLoS Genetics, 6(6). Ikram, M.K., Xueling, S, Jensen, RA, Cotch, MF, Hewitt, AW, Ikram, M.A., Wang, J.J., Klein, R., Klein, B.E.K., Breteler, M.M.B., Cheung, N, Liew, G., Mitchell, P., Uitterlinden, A.G., Rivadeneira, F., Hofman, A., Jong, P.T.V.M. de, Duijn, C.M. van, Kao, L, Cheng, CY, Smith, AV, Glazer, NL, Lumley, T, McKnight, B, Psaty, B.M., Jonasson, F, Eiriksdottir, G, Aspelund, T, Harris, T.B., Launer, L.J., Taylor, KD, Li, XH, Iyengar, SK, Xi, QS, Sivakumaran, TA, Mackey, DA, Macgregor, S, Martin, NG, Young, TL, Bis, JC, Wiggins, KL, Heckbert, SR, Hammond, CJ, Andrew, T., Fahy, S, Attia, J, Holliday, EG, Scott, R.J., Islam, FMA, Rotter, JI, McAuley, AK, Boerwinkle, E., Tai, ES, Gudnason, V, Siscovick, D.S., Vingerling, J.R. & Wong, TY (2010). Four Novel Loci (19q13, 6q24, 12q24, and 5q14) Influence the Microcirculation In Vivo. PLoS Genetics, 6(10), e Jaddoe, V.W.V.K., Duijn, C.M. van, Heijden, A.J. van der, Mackenbach, J.P., Moll, H.A., Steegers, E.A.P., Tiemeier, H.W., Uitterlinden, A.G., Verhulst, F.C. & Hofman, A. (2010). The Generation R Study: design and cohort update European Journal of Epidemiology, 25(11), Jansen, J.H.W., Jagt, O.P. van der, Punt, B.J., Verhaar, J.A.N., Leeuwen, J.P.T.M. van, Weinans, H.H. & Jahr, H. (2010). Stimulation of osteogenic differentiation in human osteoprogenitor cells by pulsed electromagnetic fields: an in vitro study. BMC Musculoskeletal Disorders, 11. Jansen, J.H.W., Eijken, M, Jahr, H., Chiba, H., Verhaar, J.A.N., Leeuwen, J.P.T.M. van & Weinans, H.H. (2010). Stretch- Induced Inhibition of Wnt/beta-Catenin Signaling in Mineralizing Osteoblasts. Journal of Orthopaedic Research, 28(3),

13 Kaur, K, Hardy, R, Ahasan, MM, Eijken, M, Leeuwen, J.P.T.M. van, Filer, A, Thomas, AM, Raza, K, Buckley, CD, Stewart, P.M., Rabbitt, EH, Hewison, M. & Cooper, MS (2010). Synergistic induction of local glucocorticoid generation by inflammatory cytokines and glucocorticoids: implications for inflammation associated bone loss. Annals of the Rheumatic Diseases, 69(6), Kerkhof, J.M., Meulenbelt, I., Carr, A, Gonzalez, A., Hart, D. t, Hofman, A., Kloppenburg, M, Lane, NE, Loughlin, J, Nevitt, MC, Pols, H.A.P., Rivadeneira, F., Slagboom, E.P., Spector, T.D., Stolk, L., Tsezou, A, Uitterlinden, A.G., Valdes, A.M. & Meurs, J.B.J. van (2010). Common genetic variation in the Estrogen Receptor Beta (ESR2) gene and osteoarthritis: results of a metaanalysis. BMC Medical Genetics, 11. Kerkhof, J.M., Bierma-Zeinstra, S.M.A., Castano Betancourt, M.C., Maat, M.P.M. de, Hofman, A., Pols, H.A.P., Rivadeneira Ramirez, F., Witteman, J.C.M., Uitterlinden, A.G. & Meurs, J.B.J. van (2010). Serum C reactive protein levels and genetic variation in the CRP gene are not associated with the prevalence, incidence or progression of osteoarthritis independent of body mass index. Annals of the Rheumatic Diseases, 69(11), Kestenbaum, B, Glazer, NL, Kottgen, A, Felix, J.F., Hwang, SJ, Liu, YM, Lohman, K, Kritchevsky, SB, Hausman, DB, Petersen, AK, Gieger, C, Ried, JS, Meitinger, T, Strom, TM, Wichmann, HE, Campbell, H, Hayward, C, Rudan, I, Boer, I.H., Psaty, B.M., Rice, KM, Chen, YDI, Li, M., Arking, DE, Boerwinkle, E., Coresh, J, Yang, QO, Levy, D., Rooij, F.J.A. van, Dehghan, A., Rivadeneira, F., Uitterlinden, A.G., Hofman, A., Duijn, C.M. van, Shlipak, M.G., Kao, WHL, Witteman, J.C.M., Siscovick, D.S. & Fox, CS (2010). Common Genetic Variants Associate with Serum Phosphorus Concentration. Journal of the American Society of Nephrology, 21(7), Koek, W.N.H., Meurs, J.B.J. van, Eerden, B.C.J. van der, Rivadeneira, F., Zillikens, M.C., Hofman, A., Obermayer-Pietsch, B, Lips, P., Pols, H.A., Uitterlinden, A.G. & Leeuwen, J.P.T.M. van (2010). The T-13910C Polymorphism in the Lactase Phlorizin Hydrolase Gene Is Associated With Differences in Serum Calcium Levels and Calcium Intake. Journal of Bone and Mineral Research, 25(9), Kolodkin, AN, Bruggeman, FJ, Plant, N, Mone, M.J., Bakker, BM, Campbell, M.J., Leeuwen, J.P.T.M. van, Carlberg, C, Snoep, JL & Westerhoff, HV (2010). Design principles of nuclear receptor signaling: how complex networking improves signal transduction. Molecular Systems Biology, 6. Kottgen, A, Pattaro, C, Boger, CA, Fuchsberger, C, Olden, M, Glazer, NL, Parsa, A, Gao, XY, Yang, Q, Smith, AV, O'Connell, JR, Li, M., Schmidt, H., Tanaka, T, Isaacs, A, Ketkar, S., Hwang, SJ, Johnson, AD, Dehghan, A., Teumer, A, Pare, G, Atkinson, EJ, Zeller, T, Lohman, K, Cornelis, MC, Probst-Hensch, NM, Kronenberg, F, Tonjes, A, Hayward, C, Aspelund, T, Eiriksdottir, G, Launer, L.J., Harris, T.B., Rampersaud, E, Mitchell, B.D., Arking, DE, Boerwinkle, E., Struchalin, M, Cavalieri, M, Singleton, A., Giallauria, F, Metter, J, Boer, I.H., Haritunians, T, Lumley, T, Siscovick, D, Psaty, B.M., Zillikens, M.C., Oostra, B.A., Feitosa, M, Province, M, Andrade, M de, Turner, ST, Schillert, A, Ziegler, A, Wild, PS, Schnabel, RB, Wilde, S, Munzel, T, Leak, TS, Illig, T, Klopp, N, Meisinger, C, Wichmann, HE, Koenig, W., Zgaga, L, Zemunik, T, Kolcic, I, Minelli, C, Hu, FB, Johansson, A, Igl, W, Zaboli, G, Wild, SH, Wright, AF, Campbell, H, Ellinghaus, D, Schreiber, S., Aulchenko, Y.S., Felix, J.F., Rivadeneira Ramirez, F., Uitterlinden, A.G., Hofman, A., Imboden, M, Nitsch, D, Brandstatter, A, Kollerits, B, Kedenko, L, Magi, R, Stumvoll, M., Kovacs, P, Boban, M, Campbell, S, Endlich, K, Volzke, H, Kroemer, HK, Nauck, M., Volker, U, Polasek, O, Vitart, V, Badola, S, Parker, AN, Ridker, P.M., Kardia, SLR, Blankenberg, S, Liu, YM, Curhan, GC, Franke, A, Rochat, T, Paulweber, B, Prokopenko, I, Wang, W., Gudnason, V, Shuldiner, AR, Coresh, J, Schmidt, R., Ferrucci, L, Shlipak, M.G., Duijn, C.M. van, Borecki, I, Kramer, BK, Rudan, I, Gyllensten, U, Wilson, JF, Witteman, J.C.M., Pramstaller, P.P., Rettig, R, Hastie, N, Chasman, DI, Kao, WH, Heid, IM & Fox, CS (2010). New loci associated with kidney function and chronic kidney disease. Nature Genetics, 42(5), 376-U34. Liu, F., Wollstein, A.D., Hysi, PG, Ankra-Badu, GA, Spector, T.D., Park, D, Larsson, M., Duffy, DL, Montgomery, GW, Mackey, DA, Walsh, S., Lao Grueso, O., Hofman, A., Rivadeneira Ramirez, F., Vingerling, J.R., Uitterlinden, A.G., Martin, NG, Hammond, CJ, Kayser, M. & Zhu, G (2010). Digital Quantification of Human Eye Color Highlights Genetic Association of Three New Loci. PLoS Genetics, 6(5). Meyer, TE, Verwoert, G.C., Hwang, SJ, Glazer, NL, Smith, AV, Rooij, F.J.A. van, Ehret, GB, Boerwinkle, E., Felix, J.F., Leak, TS, Harris, T.B., Yang, Q, Dehghan, A., Aspelund, T, Katz, R, Homuth, G., Kocher, T, Rettig, R, Ried, JS, Gieger, C, Prucha, H, Pfeufer, A, Meitinger, T, Coresh, J, Hofman, A., Sarnak, MJ, Chen, YDI, Uitterlinden, A.G., Chakravarti, A, Psaty, B.M., Duijn, C.M. van, Kao, WHL, Witteman, J.C.M., Gudnason, V, Siscovick, D.S., Fox, CS & Kottgen, A (2010). Genome-Wide Association Studies of Serum Magnesium, Potassium, and Sodium Concentrations Identify Six Loci Influencing Serum Magnesium Levels. PLoS Genetics, 6(8). Mihaescu, R., Zitteren, M. van, Hoek, M. van der, Sijbrands, E.J.G., Uitterlinden, A.G., Witteman, J.C.M., Hofman, A., Hunink, M.G.M., Duijn, C.M. van & Janssens, A.C.J.W. (2010). Improvement of Risk Prediction by Genomic Profiling: Reclassification Measures Versus the Area Under the Receiver Operating Characteristic Curve. American Journal of Epidemiology, 172(3), Monraats, PS, Fang, Y., Pons, D., Pires, NMM, Pols, H.A.P., Zwinderman, A.H., Maat, M.P.M. de, Doevendans, PAF, Dewinter, RJ, Tio, R.A., Waltenberger, J, Frants, R.R., Quax, PHA, Laarse, A. van der, Wall, E.E. van der, Uitterlinden, A.G. & Jukema, J.W. (2010). Vitamin D receptor: a new risk marker for clinical restenosis after percutaneous coronary intervention. Expert Opinion on Therapeutic Targets, 14(3), Morrison, AC, Felix, J.F., Cupples, L.A., Glazer, NL, Loehr, LR, Dehghan, A., Demissie, S, Bis, JC, Rosamond, WD, Aulchenko, Y.S., Wang, YA, Haritunians, T, Folsom, A.R., Rivadeneira, F., Benjamin, EJ, Lumley, T, Couper, D, Stricker, B.H.C., O'Donnell, CJ, Rice, KM, Chang, PP, Hofman, A., Levy, D., Rotter, JI, Fox, ER, Uitterlinden, A.G., Wang, T.J., Psaty, B.M., Willerson, J.T., Duijn, C.M. van, Boerwinkle, E., Witteman, J.C.M., Vasan, RS & Smith, NL (2010). Genomic Variation Associated With Mortality Among Adults of European and African Ancestry With Heart Failure The Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium. Circulation-cardiovascular genetics, 3(3), 248-U64. 79

14 Nettleton, J.A., McKeown, N.M., Kanoni, S, Lemaitre, R.N., Ngwa, J, Rooij, F.J.A. van, Sonestedt, E, Wojczynski, M.K., Ye, Z & Tanaka, T (2010). Interactions of dietary whole-grain intake with fasting glucose- and insulin-related genetic loci in individuals of European descent. Diabetes Care, 33, Newman, AB, Walter, S., Lunetta, KL, Garcia, ME, Slagboom, P.E., Christensen, K., Arnold, AM, Aspelund, T, Aulchenko, Y.S., Benjamin, EJ, Christiansen, L, D'Agostino, RB, Fitzpatrick, AL, Franceschini, N, Glazer, NL, Gudnason, V, Hofman, A., Kaplan, R, karasik, D., Kelly-Hayes, M, Kiel, DP, Launer, L.J., Marciante, KD, Massaro, JM, Miljkovic, I, Nalls, MA, Hernandez, D., Psaty, B.M., Rivadeneira, F., Rotter, J, Seshadri, S, Smith, AV, Taylor, KD, Tiemeier, H.W., Uh, HW, Uitterlinden, A.G., Vaupel, JW, Walston, J, Westendorp, R.G.J., Harris, T.B., Lumley, T, Duijn, C.M. van & Murabito, JM (2010). A Meta-analysis of Four Genome-Wide Association Studies of Survival to Age 90 Years or Older: The Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium. Journals of Gerontology Series A-Biological Sciences and Medical Sciences, 65(5), Noord, C. van, Dorr, M, Sturkenboom, M.C.J.M., Straus, S.M.J.M., Reffelmann, T, Felix, SB, Hofman, A., Kors, J.A., Haring, R, Jong, F.H. de, Nauck, M., Uitterlinden, A.G., Wallaschofski, H., Witteman, J.C.M., Volzke, H & Stricker, B.H.C. (2010). The association of serum testosterone levels and ventricular repolarization. European Journal of Epidemiology, 25(1), O'Seaghdha, CM, Yang, QO, Glazer, NL, Leak, TS, Dehghan, A., Smith, AV, Kao, WHL, Lohman, K, Hwang, SJ, Johnson, AD, Hofman, A., Uitterlinden, A.G., Chen, YDI, Brown, EM, Siscovick, D.S., Harris, T.B., Psaty, B.M., Coresh, J, Gudnason, V, Witteman, J.C.M., Liu, YM, Kestenbaum, BR, Fox, CS & Kottgen, A (2010). Common variants in the calcium-sensing receptor gene are associated with total serum calcium levels. Human Molecular Genetics, 19(21), Pfeufer, A, Noord, C. van, Marciante, KD, Arking, DE, Larson, MG, Smith, AV, Tarasov, KV, Muller, M., Sotoodehnia, N, Sinner, MF, Verwoert, G.C., Li, M., Kao, WHL, Kottgen, A, Coresh, J, Bis, JC, Psaty, B.M., Rice, K, Rotter, JI, Rivadeneira, F., Hofman, A., Kors, J.A., Stricker, B.H.C., Uitterlinden, A.G., Duijn, C.M. van, Beckmann, BM, Sauter, W, Gieger, C, Lubitz, SA, Newton- Cheh, C, Wang, T.J., Magnani, JW, Schnabel, RB, Chung, MK, Barnard, J, Smith, JD, Wagoner, DR Van, Vasan, RS, Aspelund, T, Eiriksdottir, G, Harris, T.B., Launer, L.J., Najjar, SS, Lakatta, E, Schlessinger, D, Uda, M, Abecasis, GR, Muller- Myhsok, B, Ehret, GB, Boerwinkle, E., Chakravarti, A, Soliman, EZ, Lunetta, KL, Perz, S, Wichmann, HE, Meitinger, T, Levy, D., Gudnason, V, Ellinor, PT, Sanna, S, Kaab, S, Witteman, J.C.M., Alonso, A., Benjamin, EJ & Heckbert, SR (2010). Genome-wide association study of PR interval. Nature Genetics, 42(2), 153-U89. Ramdas, W.D., Koolwijk, L.M.E. van, Ikram, M.K., Jansonius, N.M., Jong, P.T.V.M. de, Bergen, A.A.B., Isaacs, A.J., Amin, N., Aulchenko, Y.S., Wolfs, R.C.W., Hofman, A., Rivadeneira, F., Oostra, B.A., Uitterlinden, A.G., Hysi, P, Hammond, CJ, Lemij, H.G., Vingerling, J.R., Klaver, C.C.W. & Duijn, C.M. van (2010). A Genome-Wide Association Study of Optic Disc Parameters. PLoS Genetics, 6(6). Reiling, E, Jafar-Mohammadi, B, Riet, E van, Weedon, MN, Vliet-Ostaptchouk, JV van, Hansen, T., Saxena, R., Haeften, T.W. van, Arp, PA, Das, S., Nijpels, G., Groenewoud, MJ, Hove, EC van, Uitterlinden, A.G., Smit, J.W.A., Morris, A.D., Doney, ASF, Palmer, CNA, Guiducci, C, Hattersley, A.T., Frayling, T.M., Pedersen, O, Slagboom, P.E., Altshuler, DM, Groop, L, Romijn, J.A., Maassen, J.A., Hofker, MH, Dekker, J.M., McCarthy, MI & Hart, L.M. 't (2010). Genetic association analysis of LARS2 with type 2 diabetes. Diabetologia, 53(1), Reiling, E, Ling, C, Uitterlinden, A.G., Riet, E van, Welschen, LMC, Ladenvall, C, Almgren, P, Lyssenko, V, Nijpels, G., Hove, EC van, Maassen, J.A., Geus, E.J.C. de, Boomsma, D.I., Dekker, J.M., Groop, L, Willemsen, G & Hart, L.M. 't (2010). The Association of Mitochondrial Content with Prevalent and Incident Type 2 Diabetes. Journal of Clinical Endocrinology and Metabolism, 95(4), Rodenburg, E.M., Visser, L.E., Danser, A.H.J., Hofman, A., Noord, C. van, Witteman, J.C.M., Uitterlinden, A.G. & Stricker, B.H.C. (2010). Genetic variance in CYP2C8 and increased risk of myocardial infarction. Pharmacogenetics Genomics, 20(7), Seshadri, S, Fitzpatrick, AL, Ikram, M.A., DeStefano, AL, Gudnason, V, Boada, M, Bis, JC, Smith, AV, Carassquillo, MM, Lambert, JC, Harold, D, Schrijvers, E.M.C., Ramirez-Lorca, R, Debette, S, Longstreth, W.T., Janssens, A.C.J.W., Pankratz, VS, Dartigues, J.F., Hollingworth, P, Aspelund, T, Hernandez, I, Beiser, A, Kuller, LH, Koudstaal, P.J., Dickson, DW, Tzourio, C., Abraham, R, Antunez, C, Du, YC, Rotter, JI, Aulchenko, Y.S., Harris, T.B., Petersen, R.C., Berr, C, Owen, M.J., Lopez-Arrieta, J, Varadarajan, BN, Becker, JT, Rivadeneira, F., Nalls, MA, Graff-Radford, NR, Campion, D, Auerbach, S, Rice, K, Hofman, A., Jonsson, PV, Schmidt, H., Lathrop, M, Mosley, TH, Psaty, B.M., Uitterlinden, A.G., Farrer, L.A., Lumley, T, Ruiz, A., Williams, J., Amouyel, P, Younkin, SG, Wolf, PA, Launer, L.J., Lopez, OL, Duijn, C.M. van & Breteler, M.M.B. (2010). Genome-wide Analysis of Genetic Loci Associated With Alzheimer Disease. Jama - Journal of the American Medical Association, 303(18), Siemes, C., Visser, L.E., Jong, F.H. de, Coebergh, J.W.W., Uitterlinden, A.G., Hofman, A., Stricker, B.H.C. & Schaik, R.H.N. van (2010). Cytochrome P450 3A gene variation, steroid hormone serum levels and prostate cancer-the Rotterdam Study. Steroids, 75(12), Smedts, H.P.M., Isaacs, A.J., Costa, D. de, Uitterlinden, A.G., Duijn, C.M. van, Groot, A.C. de, Helbing, W.A., Steegers, E.A.P. & Steegers-Theunissen, R.P.M. (2010). VEGF Polymorphisms Are Associated With Endocardial Cushion Defects: A Family- Based Case-Control Study. Pediatric Research, 67(1), Smith, NL, Felix, J.F., Morrison, AC, Demissie, S, Glazer, NL, Loehr, LR, Cupples, L.A., Dehghan, A., Lumley, T, Rosamond, WD, Lieb, W, Rivadeneira, F., Bis, JC, Folsom, A.R., Benjamin, E, Aulchenko, Y.S., Haritunians, T, Couper, D, Murabito, J, Wang, YA, Stricker, B.H.C., Gottdiener, JS, Chang, PP, Wang, T.J., Rice, KM, Hofman, A., Heckbert, SR, Fox, ER, O'Donnell, CJ, Uitterlinden, A.G., Rotter, JI, Willerson, J.T., Levy, D., Duijn, C.M. van, Psaty, B.M., Witteman, J.C.M., Boerwinkle, E. & Vasan, RS (2010). Association of Genome-Wide Variation With the Risk of Incident Heart Failure in Adults of European and African Ancestry A Prospective Meta-Analysis From the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium. Circulation-cardiovascular genetics, 3(3), 256-U79. 80

15 Smith, NL, Chen, MH, Dehghan, A., Strachan, DP, Basu, S., Soranzo, N, Hayward, C, Rudan, I, Sabater-Lleal, M, Bis, JC, Maat, M.P.M. de, Rumley, A, Kong, XX, Yang, Q, Williams, FMK, Vitart, V, Campbell, H, Malarstig, A, Wiggins, KL, Duijn, C.M. van, McArdle, WL, Pankow, JS, Johnson, AD, Silveira, A, McKnight, B, Uitterlinden, A.G., Aleksic, N, Meigs, JB, Peters, A., Koenig, W., Cushman, M., Kathiresan, S, Rotter, JI, Bovill, EG, Hofman, A., Boerwinkle, E., Tofler, GH, Peden, JF, Psaty, B.M., Leebeek, F.W.G., Folsom, A.R., Larson, MG, Spector, T.D., Wright, AF, Wilson, JF, Hamsten, A., Lumley, T, Witteman, J.C.M., Tang, WH & O'Donnell, CJ (2010). Novel Associations of Multiple Genetic Loci With Plasma Levels of Factor VII, Factor VIII, and von Willebrand Factor The CHARGE (Cohorts for Heart and Aging Research in Genome Epidemiology) Consortium. Circulation, 121(12), 1382-U45. Sniekers, Y.H., Osch, G.J.V.M. van, Jahr, H., Weinans, H.H. & Leeuwen, J.P.T.M. van (2010). Estrogen Modulates Iodoacetate- Induced Gene Expression in Bovine Cartilage Explants. Journal of Orthopaedic Research, 28(5), Solouki, A., Verhoeven, V.J.M., Duijn, C.M. van, Verkerk, A.J.M.H., Ikram, M.K., Hysi, PG, Despriet, D.D.G., Koolwijk, L.M.E. van, Ho, L., Ramdas, W.D., Czudowska, M.A., Kuijpers, R.W.A.M., Amin, N., Struchalin, M, Aulchenko, Y.S., Rij, G. van, Riemslag, FCC, Young, TL, Mackey, DA, Spector, T.D., Gorgels, T.G.M.F., Willemse-Assink, JJM, Isaacs, A.J., Kramer, R, Swagemakers, S.M.A., Bergen, A.A.B., Oosterhout, A.A.L.J. van, Oostra, B.A., Rivadeneira, F., Uitterlinden, A.G., Hofman, A., Jong, P.T.V.M. de, Hammond, CJ, Vingerling, J.R. & Klaver, C.C.W. (2010). A genome-wide association study identifies a susceptibility locus for refractive errors and myopia at 15q14. Nature Genetics, 42(10), Sotoodehnia, N, Isaacs, A.J., Bakker, PIW de, Dorr, M, Newton-Cheh, C, Nolte, I.M., Harst, P. van der, Muller, M., Eijgelsheim, M., Alonso, A., Hicks, AA, Padmanabhan, S, Hayward, C, Smith, AV, Polasek, O, Giovannone, S, Fu, JY, Magnani, JW, Marciante, KD, Pfeufer, A, Gharib, SA, Teumer, A, Li, M., Bis, JC, Rivadeneira, F., Aspelund, T, Kottgen, A, Johnson, T, Rice, K, Sie, M.P.S., Wang, YA, Klopp, N, Fuchsberger, C, Wild, SH, Leach, IM, Estrada, K, Volker, U, Wright, AF, Asselbergs, F.W., Qu, JX, Chakravarti, A, Sinner, MF, Kors, J.A., Petersmann, A, Harris, T.B., Soliman, EZ, Munroe, PB, Psaty, B.M., Oostra, B.A., Cupples, L.A., Perz, S, Boer, R.A. de, Uitterlinden, A.G., Volzke, H, Spector, T.D., Liu, FY, Boerwinkle, E., Dominiczak, AF, Rotter, JI, Herpen, G. van, Levy, D., Wichmann, HE, Gilst, W.H. van, Witteman, J.C.M., Kroemer, HK, Kao, WHL, Heckbert, SR, Meitinger, T, Hofman, A., Campbell, H, Folsom, A.R., Veldhuisen, D.J., Schwienbacher, C, O'Donnell, CJ, Volpato, CB, Caulfield, MJ, Connell, JM, Launer, L, Lu, XW, Franke, L, Fehrmann, RSN, Meerman, GT, Groen, H.J.M., Weersma, RK, Berg, L.H. van den, Wijmenga, C., Ophoff, R.A., Navis, G, Rudan, I, Snieder, H, Wilson, JF, Pramstaller, P.P., Siscovick, D.S., Wang, T.J., Gudnason, V, Duijn, C.M. van, Felix, SB, Fishman, GI & Jamshidi, Y (2010). Common variants in 22 loci are associated with QRS duration and cardiac ventricular conduction. Nature Genetics, 42(12), Speliotes, EK, Willer, CJ, Berndt, SI, Monda, KL, Thorleifsson, G, Jackson, AU, Allen, HL, Lindgren, CM, Luan, J, Magi, R, Randall, JC, Vedantam, S, Winkler, TW, Qi, L., Workalemahu, T, Heid, IM, Steinthorsdottir, V, Stringham, HM, Weedon, MN, Wheeler, E, Wood, AR, Ferreira, T, Weyant, RJ, Segre, AV, Estrada, K, Liang, LM, Nemesh, J, Park, JH, Gustafsson, S, Kilpelanen, TO, Yang, JA, Bouatia-Naji, N, Esko, T, Feitosa, MF, Kutalik, Z, Mangino, M, Raychaudhuri, S, Scherag, A, Smith, AV, Welch, R, Zhao, JH, Aben, KK, Absher, DM, Amin, N., Dixon, AL, Fisher, E, Glazer, NL, Goddard, ME, Heard-Costa, NL, Hoesel, V, Hottenga, J.J., Johansson, A, Johnson, T, Ketkar, S., Lamina, C, Li, SX, Moffatt, MF, Myers, R.H., Narisu, N, Perry, JRB, Peters, M.J., Preuss, M, Ripatti, S, Rivadeneira Ramirez, F., Sandholt, C, Scott, LJ, Timpson, NJ, Tyrer, JP, Wingerden, S van, Watanabe, RM, White, CC, Wiklund, F, Barlassina, C, Chasman, DI, Cooper, MN, Jansson, JO, Lawrence, RW, Pellikka, N, Prokopenko, I, Shi, JX, Thiering, E, Alavere, H, Alibrandi, MTS, Almgren, P, Arnold, AM, Aspelund, T, Atwood, LD, Balkau, B, Balmforth, AJ, Bennett, AJ, Ben-Shlomo, Y, Bergman, RN, Bergmann, S, Biebermann, H., Blakemore, AIF, Boes, T, Bonnycastle, LL, Bornstein, S.R., Brown, MJ, Buchanan, TA, Busonero, F, Campbell, H, Cappuccio, F.P., Cavalcanti-Proenca, C, Chen, YDI, Chen, C.M., Chines, PS, Clarke, R., Coin, L, Connell, J., Day, INM, Heijer, M. den, Duan, JB, Ebrahim, S, Elliott, P., Elosua, R, Eiriksdottir, G, Erdos, MR, Eriksson, JG, Facheris, MF, Felix, SB, Fischer-Posovszky, P, Folsom, A.R., Friedrich, N, Freimer, N.B., Fu, M, Gaget, S, Gejman, PV, Geus, E.J.C. de, Gieger, C, Gjesing, AP, Goel, A, Goyette, P, Grallert, H, Grassler, J, Greenawalt, DM, Groves, CJ, Gudnason, V, Guiducci, C, Hartikainen, AL, Hassanali, N, Hall, AS, Havulinna, AS, Hayward, C, Heath, AC, Hengstenberg, C, Hicks, AA, Hinney, A, Hofman, A., Homuth, G., Hui, J, Igl, W, Iribarren, C, Isomaa, B, Jacobs, KB, Jarick, I, Jewell, E, John, U, Jorgensen, T, Jousilahti, P, Jula, A, Kaakinen, M, Kajantie, E, Kaplan, LM, Kathiresan, S, Kettunen, J, Kinnunen, L, Knowles, JW, Kolcic, I, Konig, IR, Koskinen, S, Kovacs, P, Kuusisto, J, Kraft, P, Kvaloy, K, Laitinen, J, Lantieri, O, Lanzani, C, Launer, L.J., Lecoeur, C, Lehtimaki, T, Lettre, G., Liu, JJ, Lokki, ML, Lorentzon, M, Luben, RN, Ludwig, B., Manunta, P, Marek, D, Marre, M., Martin, NG, McArdle, WL, McCarthy, A, McKnight, B, Meitinger, T, Melander, O, Meyre, D, Midthjell, K, Montgomery, GW, Morken, MA, Morris, AP, Mulic, R, Ngwa, JS, Nelis, M, Neville, MJ, Nyholt, DR, O'Donnell, CJ, O'Rahilly, S, Ong, KK, Oostra, B.A., Pare, G, Parker, AN, Perola, M, Pichler, I, Pietilainen, KH, Platou, CGP, Polasek, O, Pouta, A, Rafelt, S, Raitakari, O, Rayner, NW, Ridderstrale, M, Rief, W, Ruokonen, A, Robertson, NR, Rzehak, P, Salomaa, V, Sanders, AR, Sandhu, MS, Sanna, S, Saramies, J, Savolainen, MJ, Scherag, S, Schipf, S, Schreiber, S., Schunkert, H., Silander, K, Sinisalo, J, Siscovick, D.S., Smit, J.H., Soranzo, N, Sovio, U, Stephens, J, Surakka, I, Swift, AJ, Tammesoo, ML, Tardif, JC, Teder-Laving, M, Teslovich, TM, Thompson, JR, Thomson, B, Tonjes, A, Tuomi, T, Meurs, J.B.J. van, Ommen, G.J. van, Vatin, V, Viikari, J, Visvikis-Siest, S, Vitart, V, Vogel, CIG, Voight, BF, Waite, LL, Wallaschofski, H., Walters, GB, Widen, E, Wiegand, S, Wild, SH, Willemsen, G, Witte, DR, Witteman, J.C.M., Xu, J.F., Zhang, QY, Zgaga, L, Ziegler, A, Zitting, P, Beilby, JP, Farooqi, IS, Hebebrand, J., Huikuri, HV, James, AL, Kahonen, M, Levinson, DF, Macciardi, F, Nieminen, MS, Ohlsson, C, Palmer, LJ, Ridker, P.M., Stumvoll, M., Beckmann, J.S., Boeing, H., Boerwinkle, E., Boomsma, D.I., Caulfield, MJ, Chanock, SJ, Collins, FS, Cupples, L.A., Smith, G.D., Erdmann, J., Froguel, P, Gronberg, H, Gyllensten, U, Hall, P., Hansen, T., Harris, T.B., Hattersley, A.T., Hayes, RB, Heinrich, J., Hu, FB, Hveem, K, Illig, T, Jarvelin, MR, Kaprio, J, Karpe, F, Khaw, KT, Kiemeney, LA, Krude, H., Laakso, M., Lawlor, DA, Metspalu, A, Munroe, PB, Ouwehand, WH, Pedersen, O, Penninx, BW, Peters, A., Pramstaller, P.P., Quertermous, T, Reinehr, T, Rissanen, A, Rudan, I, Samani, NJ, Schwarz, PEH, Shuldiner, AR, Spector, T.D., Tuomilehto, J, Uda, M, Uitterlinden, A.G., Valle, TT, Wabitsch, M, Waeber, G, Wareham, NJ, Watkins, H, Wilson, JF, Wright, AF, Zillikens, M.C., Chatterjee, N, McCarroll, SA, Purcell, S, Schadt, EE, Visscher, P.M., Assimes, TL, Borecki, IB, Deloukas, P, Fox, CS, Groop, LC, Haritunians, T, Hunter, DJ, Kaplan, RC, Mohlke, KL, O'Connell, JR, Peltonen, L., Schlessinger, D, Strachan, DP, Duijn, C.M. van, Wichmann, HE, Frayling, T.M., Thorsteinsdottir, U, Abecasis, GR, Barroso, I, Boehnke, M, Stefansson, K, North, KE, McCarthy, MI, Hirschhorn, JN, Ingelsson, E & Loos, RJF (2010). Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index. Nature Genetics, 42(11), 937-U53. Teslovich, TM, Musunuru, K, Smith, AV, Edmondson, AC, Stylianou, IM, Koseki, M, Pirruccello, JP, Ripatti, S, Chasman, DI, Willer, CJ, Johansen, CT, Fouchier, SW, Isaacs, A, Peloso, GM, Barbalic, M, Ricketts, SL, Bis, JC, Aulchenko, Y.S., Thorleifsson, G, Feitosa, MF, Chambers, J, Orho-Melander, M, Melander, O, Johnson, T, Li, XH, Guo, XQ, Li, MY, Cho, YS, Go, 81

16 MJ, Kim, YJ, Lee, JY, Park, T, Kim, K., Sim, X, Ong, RTH, Croteau-Chonka, DC, Lange, LA, Smith, JD, Song, K, Zhao, JH, Yuan, X, Luan, JA, Lamina, C, Ziegler, A, Zhang, W, Zee, RYL, Wright, AF, Witteman, J.C.M., Wilson, JF, Willemsen, G, Wichmann, HE, Whitfield, JB, Waterworth, D.M., Wareham, NJ, Waeber, G, Vollenweider, P, Voight, BF, Vitart, V, Uitterlinden, A.G., Uda, M, Tuomilehto, J, Thompson, JR, Tanaka, T, Surakka, I, Stringham, HM, Spector, T.D., Soranzo, N, Smit, J.H., Sinisalo, J, Silander, K, Sijbrands, E.J.G., Scuteri, A, Scott, J, Schlessinger, D, Sanna, S, Salomaa, V, Saharinen, J, Sabatti, C, Ruokonen, A, Rudan, I, Rose, LM, Roberts, R., Rieder, M, Psaty, B.M., Pramstaller, P.P., Pichler, I, Perola, M, Penninx, BWJH, Pedersen, NL, Pattaro, C, Parker, AN, Pare, G, Oostra, B.A., O'Donnell, CJ, Nieminen, MS, Nickerson, DA, Montgomery, GW, Meitinger, T, McPherson, R, McCarthy, MI, McArdle, W, Masson, D, Martin, NG, Marroni, F, Mangino, M, Magnusson, PKE, Lucas, G, Luben, R, Loos, RJF, Lokki, ML, Lettre, G., Langenberg, C, Launer, L.J., Lakatta, EG, Laaksonen, R, Kyvik, KO, Kronenberg, F, Konig, IR, Khaw, KT, Kaprio, J, Kaplan, LM, Johansson, A, Jarvelin, MR, Janssens, A.C.J.W., Ingelsson, E, Igi, W, Hovingh, G.K., Hottenga, J.J., Hofman, A., Hicks, AA, Hengstenberg, C, Heid, IM, Hayward, C, Havulinna, AS, Hastie, ND, Harris, T.B., Haritunians, T, Hall, AS, Gyllensten, U, Guiducci, C, Groop, LC, Gonzalez, E, Gieger, C, Freimer, N.B., Ferrucci, L, Erdmann, J., Elliott, P., Ejebe, KG, Doering, A, Dominiczak, AF, Demissie, S, Deloukas, P, Geus, E.J.C. de, Faire, U de, Crawford, G, Collins, FS, Chen, YDI, Caulfield, MJ, Campbell, H, Burtt, NP, Bonnycastle, LL, Boomsma, D.I., Boekholdt, S.M., Bergman, RN, Barroso, I, Bandinelli, S, Ballantyne, C.M., Assimes, TL, Quertermous, T, Altshuler, D, Seielstad, M, Wong, TY, Tai, ES, Feranil, AB, Kuzawa, CW, Adair, LS, Taylor, HA, Borecki, IB, Gabriel, SB, Wilson, JG, Holm, H, Thorsteinsdottir, U, Gudnason, V, Krauss, RM, Mohlke, KL, Ordovas, JM, Munroe, PB, Kooner, JS, Tall, AR, Hegele, RA, Kastelein, J.J.P., Schadt, EE, Rotter, JI, Boerwinkle, E., Strachan, DP, Mooser, V, Stefansson, K, Reilly, MP, Samani, NJ, Schunkert, H., Cupples, L.A., Sandhu, MS, Ridker, P.M., Rader, DJ, Duijn, C.M. van, Peltonen, L., Abecasis, GR, Boehnke, M & Kathiresan, S (2010). Biological, clinical and population relevance of 95 loci for blood lipids. Nature, 466(7307), Thorgeirsson, TE, Gudbjartsson, DF, Surakka, I, Vink, J.M., Amin, N., Geller, F, Sulem, P, Rafnar, T, Esko, T, Walter, S., Gieger, C, Rawal, R, Mangino, M, Prokopenko, I, Magi, R, Keskitalo, K, Gudjonsdottir, IH, Gretarsdottir, S, Stefansson, H, Thompson, JR, Aulchenko, Y.S., Nelis, M, Aben, KK, Heijer, M. den, Dirksen, A., Ashraf, H, Soranzo, N, Valdes, A.M., Steves, C, Uitterlinden, A.G., Hofman, A., Tonjes, A, Kovacs, P, Hottenga, J.J., Willemsen, G, Vogelzangs, N, Doring, A, Dahmen, N, Nitz, B, Pergadia, ML, Saez, B, Diego, V De, Lezcano, V, Garcia-Prats, MD, Ripatti, S, Perola, M, Kettunen, J, Hartikainen, AL, Pouta, A, Laitinen, J, Isohanni, M, Huei-Yi, S, Allen, M, Krestyaninova, M, Hall, AS, Jones, GT, Rij, AM van, Mueller, T., Dieplinger, B, Haltmayer, M, Jonsson, S, Matthiasson, SE, Oskarsson, H, Tyrfingsson, T, Kiemeney, LA, Mayordomo, JI, Lindholt, JS, Pedersen, J.H., Franklin, WA, Wolf, H., Montgomery, GW, Heath, AC, Martin, NG, Madden, PAF, Giegling, I, Rujescu, D, Jarvelin, MR, Salomaa, V, Stumvoll, M., Spector, T.D., Wichmann, HE, Metspalu, A, Samani, NJ, Penninx, BW, Oostra, B.A., Boomsma, D.I., Tiemeier, H.W., Duijn, C.M. van, Kaprio, J, Gulcher, JR, McCarthy, MI, Peltonen, L., Thorsteinsdottir, U & Stefansson, K (2010). Sequence variants at CHRNB3-CHRNA6 and CYP2A6 affect smoking behavior. Nature Genetics, 42(5), 448-U135. Tsianos, GI, Evangelou, E, Boot, A., Zillikens, M.C., Meurs, J.B.J. van, Uitterlinden, A.G. & Ioannidis, JPA (2010). Associations of polymorphisms of eight muscle- or metabolism-related genes with performance in Mount Olympus marathon runners. Journal of Applied Physiology, 108(3), Vergeer, M, Boekholdt, S.M., Sandhu, MS, Ricketts, SL, Wareham, NJ, Brown, MJ, Faire, U de, Leander, K, Gigante, B, Kavousi, M., Hofman, A., Uitterlinden, A.G., Duijn, C.M. van, Witteman, J.C.M., Jukema, J.W., Schadt, EE, Schoot, E. van der, Kastelein, J.J.P., Khaw, KT, Dullaart, R.P.F., Tol, A. van, Trip, M.D. & Dallinga-Thie, G.M. (2010). Genetic Variation at the Phospholipid Transfer Protein Locus Affects Its Activity and High-Density Lipoprotein Size and Is a Novel Marker of Cardiovascular Disease Susceptibility. Circulation, 122(5), Voight, BF, Scott, LJ, Steinthorsdottir, V, Morris, AP, Dina, C, Welch, RP, Zeggini, E, Huth, C, Aulchenko, Y.S., Thorleifsson, G, McCulloch, LJ, Ferreira, T, Grallert, H, Amin, N., Wu, GM, Willer, CJ, Raychaudhuri, S, McCarroll, SA, Langenberg, C, Hofmann, OM, Dupuis, J, Qi, L., Segre, AV, Hoek, M. van, Navarro, P, Ardlie, K, Balkau, B, Benediktsson, R, Bennett, AJ, Blagieva, R, Boerwinkle, E., Bonnycastle, LL, Bostrom, KB, Bravenboer, B, Bumpstead, S, Burtt, NP, Charpentier, G, Chines, PS, Cornelis, M, Couper, DJ, Crawford, G, Doney, ASF, Elliott, KS, Elliott, AL, Erdos, MR, Fox, CS, Franklin, CS, Ganser, M, Gieger, C, Grarup, N, Green, T, Griffin, S., Groves, CJ, Guiducci, C, Hadjadj, S, Hassanali, N, Herder, C. den, Isomaa, B, Jackson, AU, Johnson, PRV, Jorgensen, T, Kao, WHL, Klopp, N, Kong, A, Kraft, P, Kuusisto, J, Lauritzen, T, Li, M., Lieverse, A, Lindgren, CM, Lyssenko, V, Marre, M., Meitinger, T, Midthjell, K, Morken, MA, Narisu, N, Nilsson, P, Owen, KR, Payne, F, Perry, JRB, Petersen, AK, Platou, C, Proenca, C, Prokopenko, I, Rathmann, W, Rayner, NW, Robertson, NR, Rocheleau, G, Roden, M, Sampson, MJ, Saxena, R., Shields, BM, Shrader, P, Sigurdsson, G, Sparso, T, Strassburger, K, Stringham, HM, Sun, Q, Swift, AJ, Thorand, B, Tichet, J, Tuomi, T, Dam, RM van, Haeften, T.W. van, Herpt, T van, Vliet-Ostaptchouk, JV van, Walters, GB, Weedon, MN, Wijmenga, C., Witteman, J.C.M., Bergman, RN, Cauchi, S, Collins, FS, Gloyn, AL, Gyllensten, U, Hansen, T., Hide, WA, Hitman, GA, Hofman, A., Hunter, DJ, Hveem, K, Laakso, M., Mohlke, KL, Morris, A.D., Palmer, CNA, Pramstaller, P.P., Rudan, I, Sijbrands, E.J.G., Stein, LD, Jaakko, T, Uitterlinden, A.G., Walker, M, Wareham, NJ, Watanabe, RM, Abecasis, GR, Boehm, BO, Campbell, H, Daly, M.J., Hattersley, A.T., Hu, FB, Meigs, JB, Pankow, JS, Pedersen, O, Wichmann, HE, Barroso, I, Florez, JC, Frayling, T.M., Groop, L, Sladek, R, Thorsteinsdottir, U, Wilson, JF, Illig, T, Froguel, P, Duijn, C.M. van, Stefansson, K, Altshuler, D, Boehnke, M & McCarthy, MI (2010). Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis. Nature Genetics, 42(7), 579-U155. Vujkovic, M., Steegers, E.A.P., Meurs, J. van, Yazdapanahm, M., Rooij, IA van, Uitterlinden, A.G. & Steegers-Theunissen, R.P.M. (2010). The maternal homocysteine pathway is influenced by riboflavin intake and MTHFR polymorphisms without affecting the risk of orofacial clefts in the offspring. European Journal of Clinical Nutrition, 64(3), Winkel, M.L. te, Beek, R.D. van, Muinck Keizer-Schrama, S.M.P.F., Uitterlinden, A.G., Hop, W.C.J., Pieters, R. & Heuvel- Eibrink, M.M. van den (2010). Pharmacogenetic risk factors for altered bone mineral density and body composition in pediatric acute lymphoblastic leukemia. Haematologica, 95(5), Wockel, V.J., Alves, RDAM, Swagemakers, S.M.A., Eijken, M, Chiba, H., Eerden, B.C.J. van der & Leeuwen, J.P.T.M. van (2010). 1 alpha,25-(oh)(2)d-3 Acts in the Early Phase of Osteoblast Differentiation to Enhance Mineralization Via Accelerated Production of Mature Matrix Vesicles. Journal of Cellular Physiology, 225(2),

17 Yang, QO, Kottgen, A, Dehghan, A., Smith, AV, Glazer, NL, Chen, MH, Chasman, DI, Aspelund, T, Eiriksdottir, G, Harris, T.B., Launer, L, Nalls, M, Hernandez, D., Arking, DE, Boerwinkle, E., Grove, ML, Li, M., Kao, WHL, Chonchol, M, Haritunians, T, Li, G., Lumley, T, Psaty, B.M., Shlipak, M, Hwang, SJ, Larson, MG, O'Donnell, CJ, Upadhyay, A, Duijn, C.M. van, Hofman, A., Rivadeneira, F., Stricker, B.H.C., Uitterlinden, A.G., Pare, G, Parker, AN, Ridker, P.M., Siscovick, D.S., Gudnason, V, Witteman, J.C.M., Fox, CS & Coresh, J (2010). Multiple Genetic Loci Influence Serum Urate Levels and Their Relationship With Gout and Cardiovascular Disease Risk Factors. Circulation-cardiovascular genetics, 3(6), Zillikens, M.C., Uitterlinden, A.G., Leeuwen, J.P.T.M. van, Berends, A.L., Henneman, P., Dijk, KW van, Oostra, B.A., Duijn, C.M. van, Pols, H.A.P. & Rivadeneira Ramirez, F. (2010). The Role of Body Mass Index, Insulin, and Adiponectin in the Relation Between Fat Distribution and Bone Mineral Density. Calcified Tissue International, 86(2),

18 EMC MM Regulation of the bioactivity of thyroid hormone Programme in brief design Thyroid hormone (TH) is essential for the development of virtually all tissues. The prohormone T4 is converted by outer ring deiodination to the active hormone T3 and by inner ring deiodination to the inactive metabolite rt3. The three deiodinases (D1-3) involved are expressed in different tissues, where they play different roles in systemic and local control of T3 levels. The deiodinases are located in cell membranes with their active site exposed to the cytoplasm, while the T3 receptors (TRs) reside in the nucleus. Uptake of thyroid hormone a cross the plasma membrane is thus required for thyroid hormone action and metabolism, and is mediated by specific transporters. Recently, our group identified an important T3 transporter (MCT8) which was shown to be mutated in patients with severe psychomotor retardation and grossly elevated serum T3 levels. This project concerns the characterization of the deiodinases and transporters in human tissues as well as their importance in the regulation of the bioactivity of thyroid hormone in development and disease. In addition, the specific role of the alpha-type TR (TR ) in the tissue-specific action of thyroid hormone, particularly in the brain, is investigated. It has been shown that there is substantial variation in thyroid hormone levels between different individuals, and that minor changes in thyroid status can result in a higher risk of diseases such as cardiovascular disease and osteoporosis. This project also involves the identification of new genes involved in determining an individual s thyroid hormone set-point, and studies consequences of genetic variants in those genes on different thyroid hormone related clinical endpoints. Key figures Department SP1 SP2 SP3 SP4 Sptot T1 T2 T3 Ttot IS FS OP Ptot internal medicine 0,58 3,73 0 0,33 4,64 nuclear medicine 0, ,2 Total 0,78 3,73 0 0,33 4, Thesis Visser, W.E. (2010, juni 30). Thyroid hormone and development; the importance of transporters and deiodinases. EUR. Prom./coprom.: Prof. Dr. Ir. T.J. Visser. Artikel/Letter to the editor Abdulrahman, RM, Verloop, H, Hoftijzer, H, Verburg, E, Hovens, GC, Corssmit, EP, Reiners, C, Gelderblom, H., Pereira, AM, Kapiteijn, E., Romijn, J.A., Visser, T.J. & Smit, J.W. (2010). Sorafenib-Induced Hypothyroidism Is Associated with Increased Type 3 Deiodination. Journal of Clinical Endocrinology and Metabolism, 95(8), Benhadi, N., Fliers, E., Visser, T.J., Reitsma, J.B. & Wiersinga, W.M. (2010). Pilot study on the assessment of the setpoint of the hypothalamus-pituitary-thyroid axis in healthy volunteers. European Journal of Endocrinology, 162(2), Bolk, N., Visser, T.J., Nijman, J.M., Jongste, IJ, Tijssen, J.G.P. & Berghout, A. (2010). Effects of Evening vs Morning Levothyroxine Intake A Randomized Double-blind Crossover Trial. Archives of Internal Medicine, 170(22), Deure, W.M. van der, Peeters, R.P. & Visser, T.J. (2010). Molecular aspects of thyroid hormone transporters, including MCT8, MCT10, and OATPs, and the effects of genetic variation in these transporters. Journal of Molecular Endocrinology, 44(1), Friesema, E.C.H., Visser, W.E. & Visser, T.J. (2010). Genetics and phenomics of thyroid hormone transport by MCT8. Molecular and Cellular Endocrinology, 322(1-2), Heemstra, KA, Hoftijzer, H, Deure, W.M. van der, Peeters, R.P., Hamdy, NA, Pereira, A, Corssmit, EP, Romijn, J.A., Visser, T.J. & Smit, J.W. (2010). The Type 2 Deiodinase Thr92Ala Polymorphism Is Associated with Increased Bone Turnover and Decreased Femoral Neck Bone Mineral Density. Journal of Bone and Mineral Research, 25(6), Henrichs, J., Schokking, J.J., Schenk, JJ, Ghassabian, A., Schmidt, H.G., Visser, T.J., Hooijkaas, H., Muinck Keizer-Schrama, S.M.P.F., Hofman, A., Jaddoe, V.W.V.K., Visser, W., Steegers, E.A.P., Verhulst, F.C., Rijke, Y.B. de & Tiemeier, H.W. (2010). Maternal Thyroid Function during Early Pregnancy and Cognitive Functioning in Early Childhood: The Generation R Study. Journal of Clinical Endocrinology and Metabolism, 95(9), Ianculescu, AG, Friesema, E.C.H., Visser, T.J., Giacomini, KM & Scanlan, TS (2010). Transport of thyroid hormones is selectively inhibited by 3-iodothyronamine. Molecular BioSystems, 6(8), Moreno, JC & Visser, T.J. (2010). Genetics and phenomics of hypothyroidism and goiter due to iodotyrosine deiodinase (DEHAL1) gene mutations. Molecular and Cellular Endocrinology, 322(1-2), Paschke, R & Visser, T.J. (2010). Clinical application and consequences of molecular genetics of thyroid diseases. Molecular and Cellular Endocrinology, 322(1-2), 1-1. Trajkovic-Arsic, M, Visser, T.J., Darras, V.M., Friesema, E.C.H., Schlott, B, Mittag, J., Bauer, K. & Heuer, H. (2010). Consequences of Monocarboxylate Transporter 8 Deficiency for Renal Transport and Metabolism of Thyroid Hormones in Mice. Endocrinology, 151(2), Trajkovic-Arsic, M, Muller, J, Darras, V.M., Groba, C, Lee, S., Weih, D, Bauer, K., Visser, T.J. & Heuer, H. (2010). Impact of Monocarboxylate Transporter-8 Deficiency on the Hypothalamus-Pituitary-Thyroid Axis in Mice. Endocrinology, 151(10),

19 Visser, W.E., Wong, W.S., Mullem, A.A.A. van, Friesema, E.C.H., Geyer, J & Visser, T.J. (2010). Study of the transport of thyroid hormone by transporters of the SLC10 family. Molecular and Cellular Endocrinology, 315(1-2), Visser, W.E., Swagemakers, S.M.A., Ozgur, Z., Schot, R., Verheijen, F.W., Ijcken, W.F.J. van, Spek, P.J. van der & Visser, T.J. (2010). Transcriptional profiling of fibroblasts from patients with mutations in MCT8 and comparative analysis with the human brain transcriptome. Human Molecular Genetics, 19(21), Part of book - abstract Deure, W.M. van der, Medici, M., Peeters, R.P. & Visser, T.J. (2010). Genetic influences on thyroid function tests. In G.A. Brent (Ed.), Thyroid Function Testing (pp ). New York: Springer Verlag. 85

20 EMC MM Signalling in reproduction and ageing Programme in brief design Hormones, such as growth hormone secretagogues and members of the TGF /activin family of growth and differentiation factors play a central role in development and functioning of the organism throughout life. This program focuses on the effect of variations in signal transduction of hormones (including ghrelin and unacylated ghrelin) and TGF family members (including anti-müllerian hormone, BMPs, inhibins and activins) during foetal and postnatal development and subsequent functioning and ageing of the organism. Furthermore, effects of mutations or single nucleotide polymorphisms in enzymes involved in biosynthesis or catabolism of steroid hormones are investigated. Variations in signaling through these pathways affect the early make-up of physiological response systems that can have effects during adult life and in the ageing process. Variations in signal transduction of ligand-receptor interaction, gene expression, proliferation and apoptosis are studied; not only at the molecular and cellular level, but also at the level of the whole body in animal models of ageing, in patients and in populations of ageing men and women. Specific areas are: 1. The role of TGF family members in female ageing, oestrogen effects and age at menopause 2. The influence of gene variants in female and male physiology 3. Development of animal models for the study of the role of hormones and TGF family members in the pathophysiology of metabolism and ageing. 4. Causes and effects of changes in steroid biosynthetic pathways. 5. Evaluation of the (metabolic) role of natural and synthetic growth hormone secretatogues in peripheral tissues in vitro and in vivo. Key figures Department SP1 SP2 SP3 SP4 Sptot T1 T2 T3 Ttot IS FS OP Ptot internal medicine 2, ,88 4,84 Total 2, ,88 4, Artikel/Letter to the editor Alwani, R.A., Herder, W.W. de, Aken, M.O. van, Berge, J.H. van den, Delwel, E.J., Dallenga, A.H.G., Jong, F.H. de, Lamberts, S.W.J, Lelij, A.J. van der & Feelders, R.A. (2010). Biochemical Predictors of Outcome of Pituitary Surgery for Cushing's Disease. Neuroendocrinology, 91(2), Burgers, J.A., Lie Fong, S., Louwers, Y.V., Valkenburg, O., Jong, F.H. de, Fauser, B.C.J.M. & Laven, J.S.E. (2010). Oligoovulatory and Anovulatory Cycles in Women with Polycystic Ovary Syndrome (PCOS): What's the Difference? Journal of Clinical Endocrinology and Metabolism, 95(12), E485-E489. Chai, W., Hofland, J., Jansen, P.M., Garrelds, I.M., Vries, R.D. de, Bogaerdt, A.J. van den, Feelders, R.A., Jong, F.H. de & Danser, A.H.J. (2010). Steroidogenesis vs. steroid uptake in the heart: do corticosteroids mediate effects via cardiac mineralocorticoid receptors? Journal of Hypertension, 28(5), Delhanty, P.J.D., Sun, YX, Visser, J.A., Kerkwijk, A.J. van, Huisman, M., Ijcken, W.F.J. van, Swagemakers, S.M.A., Smith, RG, Themmen, A.P.N. & Lelij, A.J. van der (2010). Unacylated Ghrelin Rapidly Modulates Lipogenic and Insulin Signaling Pathway Gene Expression in Metabolically Active Tissues of GHSR Deleted Mice. PLoS One, 5(7). Delhanty, P.J.D., Kerkwijk, A.J. van, Huisman, M., Zande, B. van de, Verhoef-Post, M., Gauna, C., Hofland, L.J., Themmen, A.P.N. & Lelij, A.J. van der (2010). Unsaturated fatty acids prevent desensitization of the human growth hormone secretagogue receptor by blocking its internalization. American Journal of Physiology, Endocrinology and Metabolism, 299(3), E497-E505. Elks, CE, Perry, JRB, Sulem, P, Chasman, DI, Franceschini, N, He, CY, Lunetta, KL, Visser, J.A., Byrne, EM, Cousminer, DL, Gudbjartsson, DF, Esko, T, Feenstra, B., Hottenga, J.J., Koller, DL, Kutalik, Z, Lin, P, Mangino, M, Marongiu, M, McArdle, PF, Smith, AV, Stolk, L., Wingerden, S.H. van, Zhao, JH, Albrecht, E, Corre, T, Ingelsson, E, Hayward, C, Magnusson, PKE, Smith, EN, Ulivi, S, Warrington, NM, Zgaga, L, Alavere, H, Amin, N., Aspelund, T, Bandinelli, S, Barroso, I, Berenson, GS, Bergmann, S, Blackburn, H, Boerwinkle, E., Buring, JE, Busonero, F, Campbell, H, Chanock, SJ, Chen, W., Cornelis, MC, Couper, D, Coviello, AD, d'adamo, P, Faire, U de, Geus, E.J.C. de, Deloukas, P, Doring, A, Smith, G.D., Easton, D.F., Eiriksdottir, G, Emilsson, V, Eriksson, J, Ferrucci, L, Folsom, A.R., Foroud, T., Garcia, M, Gasparini, P, Geller, F, Gieger, C, Gudnason, V, Hall, P., Hankinson, SE, Ferreli, L, Heath, AC, Hernandez, DG, Hofman, A., Hu, FB, Illig, T, Jarvelin, MR, Johnson, AD, karasik, D., Khaw, KT, Kiel, DP, Kilpelainen, TO, Kolcic, I, Kraft, P, Launer, L.J., Laven, J.S.E., Li, SX, Liu, JJ, Levy, D., Martin, NG, McArdle, WL, Melbye, M, Mooser, V, Murray, JC, Murray, SS, Nalls, MA, Navarro, P, Nelis, M, Ness, AR, Northstone, K, Oostra, B.A., Peacock, M., Palmer, LJ, Palotie, A, Pare, G, Parker, AN, Pedersen, NL, Peltonen, L., Pennell, CE, Pharoah, P., Polasek, O, Plump, AS, Pouta, A, Porcu, E, Rafnar, T, Rice, JP, Ring, SM, Rivadeneira Ramirez, F., Rudan, I, Sala, C, Salomaa, V, Sanna, S, Schlessinger, D, Schork, NJ, Scuteri, A, Segre, AV, Shuldiner, AR, Soranzo, N, Sovio, U, Srinivasan, SR, Strachan, DP, Tammesoo, ML, Tikkanen, E, Toniolo, D., Tsui, K, Tryggvadottir, L, Tyrer, J, Uda, M, Dam, RM van, Meurs, J.B.J. van, Vollenweider, P, Waeber, G, Wareham, NJ, Waterworth, D.M., Weedon, MN, Wichmann, HE, Willemsen, G, Wilson, JF, Wright, AF, Young, L, Zhai, GJ, Zhuang, WV, Bierut, LJ, Boomsma, D.I., Boyd, HA, Crisponi, L, Demerath, EW, Duijn, C.M. van, Econs, M.J., Harris, T.B., Hunter, DJ, Loos, RJF, Metspalu, A, Montgomery, GW, Ridker, P.M., Spector, T.D., Streeten, EA, Stefansson, K, Thorsteinsdottir, U, Uitterlinden, A.G., Widen, E, Murabito, JM, Ong, KK & Murray, A (2010). Thirty new loci for age at menarche identified by a meta-analysis of genome-wide association studies. Nature Genetics, 42(12), 1077-U73. 86