Building a National Cohort Eric Boerwinkle; February, 2015 - PowerPoint PPT Presentation

Building a National Cohort Eric Boerwinkle; February, 2015 Precision Medicine Workshop

What is a Cohort? • Sample of people • Who share some characteristic (e.g. a place) and time frame • Cohort study – Longitudinal – Measure/monitor/estimate some things – Assess outcomes (usually in the future) • Does not have to be a representative sample, but clear eligibility criteria allow making generalizable inferences.

CHARGE (Cohorts for Heart & Aging Research in Genome Epidemiology) Consortium, N>>100,000 FHS ARIC N~9,400 N~16,000 Deeply Phenotyped Risk Factors and Disease Array Genotypes and CHS Sequence Study of Latinos N~5,000 N~16,000 MESA, FamHeart, JHS, CARDIA Jackson Heart Study n~20,000 n~5,300 *Psaty BM, O’Donnell CJ, et al. >600 Investigators, >80 Cohorts Prospective, longitudinal follow-up. Circulation CV Genetics 2009. >60 Phenotype Working Groups Deep phenotyping for RFs and outcomes. Published Collaboration Principles Similar methods and QC for phenotyping. Available DNA, RNA, blood, imaging. >370 Publications since 2008

CHARGE (Cohorts for Heart & Aging Research in Genome Epidemiology) Consortium, N>>100,000 FHS ARIC N~9,400 N~16,000 Deeply Phenotyped Risk Factors and Disease Array Genotypes and CHS Sequence Study of Latinos N~5,000 N~16,000 MESA, FamHeart, JHS, CARDIA Jackson Heart Study n~20,000 n~5,300 >600 Investigators, >80 Cohorts >60 Phenotype Working Groups Published Collaboration Principles >140 Publications since 2008

Sequencing in Cohorts • Update – WES (N=11,500)(F4) – WGS (N=5,700) – Collaborations (ESP) (N=23,000) – Strong analytic infrastructure Morrison A. Nat Genet 2013; 45: 899-901. 5 FHS: phs000651.v4.p9; CHS: phs000667.v1.p1; ARIC phs000668.v1.p1

Building a National Cohort Artist: Chuck Close Consortium Of Cohorts A National Cohort

Building A National Cohort Enhanced Opportunities Technical Challenges • Participatory • Harmonization • Enhanced phenotyping • Big Data Challenges • Storage • Platform for clinical trials • Analytics • Pilot for national health/EMRs • Connectivity • Enhanced community resources • Virtuous cycle of health care and research The CHARGE Data Commons

Clinical and Biologic Continuum of Simple/Complex and Rare/Common splice (n =1) splice (n =1) R322X (n = 22) 3 4 12 15 16 HAL Gene p = 1.2 × 10 -13 PCSK9, Cohen, 2006; PMID: 16554528 APOC3, Crosby, 2013; PMID: 24941081 Metabolite histidine NPC1L1, Stitziel, 2014; PMID: 25390462 PLA2G7, Polfus, 2015; p = 2.6 × 10 -6 p = 1.9 × 10 -5 p = 1.4 × 10 -4 Incident HF Clinical Incident CHD Endpoints Incident CKD 8

Clinical and Biologic Continuum of Simple/Complex and Rare/Common Rare Mendelian……….. ‘ Oligogenic ’ ……………. Common Complex Few Actionable Alleles Low frequency/High impact Not related to sporadic cases Missing ‘Heritability’ in a simple way Jim Lupski Richard Gibbs Eric Boerwinkle

Building a National Cohort Virtuous Cycle of Health Care and Research A National Cohort