Abstract 19115: Genome-Wide Association Study and Replication Identifies a Novel Genetic Locus for Aortic Stenosis

Introduction: Aortic stenosis (AS) is the most prevalent valvular heart disease in developed countries. Currently, the LPA locus is the only genome-wide significant susceptibility locus for AS. The identification of additional genetic loci could inform drug development for AS, a disease without effective medical therapy. Methods: We conducted a genome-wide association study for AS in the Genetic Epidemiology on Adult Health and Aging (GERA) cohort (44,703 individuals; 3,469 cases), adjusted for age, age2, and sex. A locus which demonstrated suggestive evidence of association in GERA (p < 1 х 10-6) was examined in PennCATH (5,938 individuals; 1,252 cases), UK Biobank (111,560 individuals; 535 cases), Malmo Diet and Cancer Study (16,168 individuals; 521 cases), and Umea University (839 individuals; 218 cases). Results were combined by inverse variance-weighted fixed effects meta-analysis. Further validation was performed in the CHARGE Consortium using aortic valve calcium (AVC) (6,942 individuals; 2,245 wit...