Lpa Variants And Aortic Stenosis - A Large-Scale Case-Control Study Using Electronic Health Records

Background: Elevated lipoprotein(a) levels are a causal factor for aortic stenosis (AS). However, large-scale replication of associations between LPA polymorphisms and AS, their interactions with age and sex, and the impact of multiple risk alleles, are not well established. Objectives We sought to replicate the association between LPA single nucleotide polymorphisms (SNPs) rs10455872 and rs3798220 with AS, and identify subgroups at higher risk of AS. Methods: We included 44,703 European-ancestry individuals (3,469 cases) aged u003e= 55 years from the Genetic Epidemiology Research on Aging (GERA) Cohort. Results: Both LPA SNPs were associated with AS, with a per risk allele odds ratio (OR) of 1.34 (95% confidence interval [CI] 1.23-1.47; p = 1.66 x 10-10) for rs10455872 and 1.31 (95% CI 1.09-1.58; p = 3.58 x 10-3) for rs3798220, adjusted for age, age2, and sex. Results remained significant after adjustment for risk factors. Estimates were similar for an LPA risk score. Individuals with 2 risk alleles had u003e= 2...