Abstract 9793: Pcsk9 Loss-of-function Variants, Low-density Lipoprotein Cholesterol, and Risk of Coronary Heart Disease and Stroke: Data From the REGARDS Study and CHARGE Consortium

Introduction: PCSK9 loss-of-function variants are associated with reduced low-density lipoprotein cholesterol (LDL-C) concentrations. Genetic association studies of PCSK9 loss-of-function variants allow for the examination of the effects of lifetime low LDL-C on cardiovascular outcomes. Hypothesis: PCSK9 loss-of-function variants are associated with lower concentrations of LDL-C and reduced risk of coronary heart disease (CHD) and stroke. Methods: We studied the association of PCSK9 loss-of-function Y142X and C679X nonsense variants (n=366; 2.1%) in 17,459 African Americans (AAs) and R46L missense variants (n=962; 3.1%) in 31,469 whites with LDL-C, CHD and stroke in the US-based REasons for Geographic And Racial Difference in Stroke (REGARDS) study and 8 cohorts in the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium. We combined multivariable adjusted differences in LDL-C between participants with and without PCSK9 variants across studies using inverse-variance weighted fi...