The birth of the population-based cohort studies in preventive medicine From Framingham to Värmland

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1 EpiScania Symposium Medicon Village, Lund 2 nd September 2015 The birth of the population-based cohort studies in preventive medicine From Framingham to Värmland Peter M Nilsson, MD, PhD Department of Clinical Sciences Lund University University Hospital, Malmö Sweden

2 Framingham Heart Study - since 1948 First headquarters Screening in three generations

3 Framingham Heart Study Started in 1948 Offspring Study in 1971 Third generation in 2002 FHS generation 1: n= 5209 FHS - generation 2: n= 5124 FHS generation 3: n= 4095 (2005) Framingham Offspring Study >350 publications Focus on cardiovaskular risk, genetics and biomarkers

4 Gunnar Jungner Swedish engineer, visited the US in 1950 ies

5 Mobile x-ray screening for tuberculosis X-ray device Bus for screening 1955

6 Bror Rexhed Director Medicinalstyrelsen Tage Erlander Swedish Prime Minister

7 The Värmland Health Survey Sweden s first large population-based screening study was carried out in the county of Värmland by initiative of Medicinalstyrelsen during 1962 to 1965 In total, 97,000 subjects came to the health screening (76% of all invited) Simple physical examination done. Blood samples sent on the night-train from Karlstad to Stockholm for further analyses in the new multi-analysator (Ingmar Jungner) Follow-up after 20 years (Gunnar Lindberg, LU, Sven Törnberg, KI), and 40 years (Payam Khalili, ÖU)

8 Development of new technologies for large screening studies during 1960 ies

9 Device for automatic blood analysis. Värmland Health Survey 1962 Ingmar Junger, Lab, Stockholm

10 Device for analog-digital transformation, as well as automatic Evaluation and statistics. Värmland Health Survey 1962

11 Men born in 1913 Gösta Tibblin Göteborg Tibblin G. High blood pressure in men aged 50 - a population study of men born in Acta Med Scand (Suppl.) 1967;470:1-84.

12 Uppsala Longitudinal Study of Adult Men (ULSAM), n= 2300 Bertil Hood Malmö Preventive Project (MPP), n= 33,000 Berglund G, Nilsson P, Eriksson KF, Nilsson JA, Hedblad B, Kristenson H, Lindgärde F. Long-term outcome of the Malmö preventive project: mortality and cardiovascular morbidity. J Intern Med Jan;247(1):19-29.

13 The Malmö Preventive Project (MPP) Age-cohorts at baseline screening in the MPP cohort Women Men Age Age Baseline screening in , included 22,000 middle-aged men and 11,000 women (attendance rate 72%). Follow-up in national registers is possible for years in most subjects. Berglund G, et al. 1996, 2001, Nilsson P, et al. 2002, 2003, 2004

14 MGR FOB: Folk- och Bostadsräkningen (Population censuses, for social data) MGR: Multi-generational Register (for finding first-degree relatives)

15 PKU Register and Biobank Started in 1975, kept at Karolinska Hospital, Stockholm

16 Discovery of Legionella bacteria in 1977

17 Biobanking Work Processes

18 In December 2012, decode Genetics was purchased by Amgen decode Genetics Inc. - Iceland Kári Stéfansson decode Genetics Inc. was founded in 1996 to identify human genes associated with common diseases using population studies, and apply the knowledge gained to guide the development of candidate drugs

19 Biobanking past, present and future: responsibilities and benefits University of California, San Francisco AIDS Specimen Bank - Deposits and Withdrawals December 1982-August De Souza YG, et al. AIDS. 2013;27:

20

21 UK Biobank Prospective Cohort 500,000 UK men and women aged years when recruited and assessed during Extensive baseline questions and measurements, with stored biological samples (and opportunities to add enhanced assessments in large subsets) Repeat assessments over time in subsets of the participants to allow for sources of variation General consent for follow-up through all health records and for all types of health research Sufficiently large numbers of people developing different conditions to assess causes reliably

22 Locations of UK Biobank assessment centres around the UK (with people recruited from urban and rural areas)

23 UK Biobank: 500,000 participants aged recruited in Age , , ,000 Gender Male 228,000 Female 270,000 Deprivation More 92,000 Average 166,000 Less 241,000 Generalisability (not representativeness): Heterogeneity of study population allows associations with disease to be studied reliably

24 Newer Swedish population-based studies with associated biobanks Lifegene (KI) 0-45 years EpiHealth cohort (UU, LU) years SCAPIS (HLF) CV, lung Malmö Offspring Study (LU) Family patterns BIG-3 (RS) Smoking and risk

25 Microbiota and its consequences for health - Metabolism - Obesity - Immunology - Vascular function A link to early life colonization of the GI tract of newborns during delivery Tremaroli, Bäckhed Nature 2012; 489:

26 Summary The first large-scale population-based screening study was the Framingham Heart Study (FHS), started in 1948 In Sweden, the Värmland Health Survey in 1962 and the Men born in 1913 in 1963 were two of the first large epidemiological studies The first biobanks added to large studies was the Malmö Preventive Project and the ULSAM study in Uppsala New technologies, registers for follow-up and a high attendance rate were important aspects of the early studies in Sweden The PKU register was an early national biobank initiative (1975) PN 2015

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