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Triumphs and challenges in the identification of the genetic determinants of coronary artery disease in the multi-ethnic Million Veteran Program

Tuesday, July 28, 2020 - 4:30pm

Speakers:   Themistocles Assimes, Stanford Medicine; Catherine Tcheandjieu, VA Palo Alto

Abstract:   Coronary artery disease (CAD) remains the number one cause of morbidity and mortality worldwide despite the development of several effective primary and secondary preventative therapies over the last 50 years. Genome wide association studies (GWAS) of Coronary Artery Disease (CAD) have identified ~180 autosomal susceptibility loci to date largely among European populations but also South and East Asian populations. Curiously, almost 13 years after the discovery of the first genome wide significant locus in Europeans at the 9p21 locus, no locus has reached genome wide significance among blacks and Hispanic admixed populations. We will review the results of the largest GWAS for CAD performed to date involving Europeans, African American, and Hispanic American participants of the Million Veteran Program demonstrating along the way the strengths and limitations of several established statistical algorithms in the calculation of ethnic specific heritability estimates, local ancestry estimates, and polygenic risk scores.