Genome wide association study of extreme obesity defined by electronic medical record phenotyping

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1 1 Genome wide association study of extreme obesity defined by electronic medical record phenotyping The pseudo code and flowchart for Geisinger extreme obesity cohort are below. Questions regarding this information can be directed to Craig Wood ). Pseudo code for extreme obesity phenotype Step Description 1 Identify cohort under evaluation and obtain gender, race, and date of birth 2 Exclude subjects with malignant cancer, which was identified by meeting one of the following criteria: Problem list ever includes any ICD9 code between 140.** and 209.** 4 or more inpatient or outpatient diagnoses on different days with any ICD9 code between 140.** and 209.** 3 Clean height data: Identify height measures obtained while age>=18 years old Remove height measures <36 inches or >90 inches Calculate median height for each subject Compare median height to each individual measure of each subject Remove all height measures that are >2 inches away from the median height Recalculate median height (in inches) with remaining measures. This will be referred to as MEDIAN_HEIGHT. 4 Exclude subjects that do not have MEDIAN_HEIGHT 5 Clean weight data: Identify weight measures obtained from subjects with a MEDIAN_HEIGHT while age>=18 years old and age<65 years old Remove weight measures that occurred after bariatric surgery (see codes in Appendix A) Remove weight measures <50 pounds or >700 pounds 6 Exclude subjects without any weight measures 7 Calculate BMI and clean BMI data: For each remaining weight measure, calculate BMI using MEDIAN_HEIGHT o BMI=703*(weightLBS)/(MEDIAN_HEIGHT* MEDIAN_HEIGHT) Remove BMI values <14 kg/m 2 or >90 kg/m 2 Identify the most recent valid BMI measure Limit to the BMI values that occur within the 4 years prior to the most recent valid BMI measure (include the most recent) Exclude subjects that had a pregnancy code within the 4 years prior to the most recent valid BMI measure (see codes in Appendix B) Calculate median BMI for each subject Compare median BMI to each individual measure of each subject

2 2 Remove all BMI measures that are >5 kg/m 2 away from the median BMI Remove BMI measures that occur within 30 days of the previous BMI measure 8 Exclude subjects that have <3 BMI measures remaining 9 For each subject, count the number of remaining BMI measures that fall into the following groups: BMI<20 kg/m 2 BMI>=20 kg/m 2 and <30 kg/m 2 BMI>=30 kg/m 2 and <40 kg/m 2 BMI>=40 kg/m 2 and <50 kg/m 2 BMI>=50 kg/m 2 10 Identify cases: Definite super obese (Case Type #1): 100% of BMI measures>=50 kg/m 2 Likely super obese (Case Type #2): Not Case Type 1 and >=75% of BMI measures >=50 kg/m 2 Definite morbid obese (Case Type #3): Not Case Type 1 2 and 100% of BMI measures are >=40 kg/m 2 and <50 kg/m 2 Likely morbid obese (Case Type #4): Not Case Type 1 3 and >=75% of BMI measures are >=40 kg/m 2 and <50 kg/m 2 Non specific extreme obese (Case Type #5): Not Case Type 1 4 and >=75% of BMI measures are >=40 kg/m 2 11 For the cases identified in step 10, include a flag for the following: anti psychotic medication use o users defined as having at least 2 indications of use (i.e. medication order, medication fill, active medication list) that are separated by at least 180 days at any time during or prior to the most recent BMI value o anti psychotic medication generic names are listed in Appendix C Oral steroid medication use o users defined as having at least 2 indications of use (i.e. medication order, medication fill, active medication list) that are separated by at least 180 days at any time during or prior to the most recent BMI value o oral steroids medication generic names are listed in Appendix D 12 Identify controls: Definite control (Control Type #1): 100% of BMI measures are >=20 kg/m 2 and <30 kg/m 2 Likely control (Control Type #2): Not Control Type 1 and >=75% of BMI measures are >=20 kg/m 2 and <30 kg/m 2 13 For the controls identified in step 12, include a flag for having any of the causes of unintentional weight loss identified in Appendix E.

3 3 Appendix A: Bariatric procedure codes Bariatric surgery codes identified and used for the Geisinger algorithm CPT codes: ICD9 procedure codes: Appendix B: Pregnancy codes (check these with Ryan) CPT: ? ICD9 diagnosis: 630.** 678.**, V24, V72???? ICD9 procedure: 72.* 75.*?????

4 4 Appendix C: Anti psychotic medication names Medication name Pharmacy class Pharmacy subclass CARBAMAZEPINE Antipsychotics Antipsychotics Misc. EQUETRO Antipsychotics Antipsychotics Misc. GEODON Antipsychotics Antipsychotics Misc. LATUD Antipsychotics Antipsychotics Misc. ZIPRASIDONE HCL Antipsychotics Antipsychotics Misc. FANAPT Antipsychotics Benzisoxazoles ILOPERIDONE Antipsychotics Benzisoxazoles INVEGA Antipsychotics Benzisoxazoles PALIPERIDONE Antipsychotics Benzisoxazoles RISPERDAL Antipsychotics Benzisoxazoles RISPERIDONE Antipsychotics Benzisoxazoles ASENAPINE MALEATE Antipsychotics Dibenzapines CLOZAPINE Antipsychotics Dibenzapines CLOZARIL Antipsychotics Dibenzapines LOXAPINE SUCCINATE Antipsychotics Dibenzapines LOXITANE Antipsychotics Dibenzapines OLANZAPINE Antipsychotics Dibenzapines QUETIAPINE FUMARATE Antipsychotics Dibenzapines SAPHRIS Antipsychotics Dibenzapines SEROQUEL Antipsychotics Dibenzapines ZYPREXA Antipsychotics Dibenzapines ABILIFY Antipsychotics Quinolinone Derivatives ARIPIPRAZOLE Antipsychotics Quinolinone Derivatives CHLORDIAZEPOXIDE AMITRIPTYLINE Misc. psychotherapeutic Combination Psychotherapeutics ETRAFON Misc. psychotherapeutic Combination Psychotherapeutics LIMBITROL Misc. psychotherapeutic Combination Psychotherapeutics OLANZAPINE FLUOXETINE HCL Misc. psychotherapeutic Combination Psychotherapeutics PERPHENAZINE AMITRIPTYLI Misc. psychotherapeutic Combination Psychotherapeutics SYMBYAX Misc. psychotherapeutic Combination Psychotherapeutics TRIAVIL Misc. psychotherapeutic Combination Psychotherapeutics

5 5 Appendix D: Oral steroid medication names Medication name Pharmacy class Pharmacy subclass BETAMETHASONE Corticosteroids Glucocorticosteroids BUDESONIDE Corticosteroids Glucocorticosteroids CORTEF Corticosteroids Glucocorticosteroids CORTISONE ACETATE Corticosteroids Glucocorticosteroids DECADRON Corticosteroids Glucocorticosteroids DELTASONE Corticosteroids Glucocorticosteroids DEXAMETHASONE Corticosteroids Glucocorticosteroids ENTOCORT Corticosteroids Glucocorticosteroids HYDROCORTISONE Corticosteroids Glucocorticosteroids MEDROL Corticosteroids Glucocorticosteroids METHYLPREDNISOLONE Corticosteroids Glucocorticosteroids ORAPRED Corticosteroids Glucocorticosteroids ORASONE Corticosteroids Glucocorticosteroids PREDNISOLONE Corticosteroids Glucocorticosteroids PRELONE Corticosteroids Glucocorticosteroids STERAPRED Corticosteroids Glucocorticosteroids TRIAMCINOLONE Corticosteroids Glucocorticosteroids ZEMA Corticosteroids Glucocorticosteroids

6 6 Appendix E: ICD9 codes used for causes of unintentional weight loss in controls Co morbidity ICD9 codes Protein Calorie Malnutrition 260.** 263.** Alcoholism 303.** Parkinson s Disease 332.** Anorexia 307.1* TB 010.** 018.** HIV 042.** Heart Failure 428.** COPD 491.2* Emphysema 492.** Dementia 290.**, 294.1* SEVERE depression 296.2* 296.3* Hyperthyroidism 242.** CVA 434.*1 Chronic diarrhea Malabsorption / Celiac Disease 579.** Lactose Intolerance 271.3* Inflammatory bowel disease 555.** 556.** Chronic liver disease / Cirrhosis 571.2, 571.5, End stage kidney disease 585.6* Dysphagia , 787.2* SLE/ Lupus 695.4* Pancreatitis 557.0* 557.1* On problem list or 4+ diagnoses on different days from OP /IP encounters

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