Genome-wide association analyses using electronic health records identify new loci influencing blood pressure variation.

Abstract

Longitudinal electronic health records on 99,785 Genetic Epidemiology Research on Adult Health and Aging (GERA) cohort individuals provided 1,342,814 systolic and diastolic blood pressure measurements for a genome-wide association study on long-term average systolic, diastolic, and pulse pressure. We identified 39 novel among 75 significant loci (P≤5×10−8), most replicating in the combined International Consortium for Blood Pressure (ICBP, n=69,396) and UK Biobank (UKB, n=152,081) studies. Combining GERA with ICBP yielded 36 additional novel loci, most replicating in UKB. Combining all three studies (n=321,262) yielded 241 additional genome-wide significant loci, although for these no replication sample was available. All associated loci explained 2.9%/2.5%/3.1% of systolic/diastolic/pulse pressure variation in GERA non-Hispanic whites. Using multiple BP measurements in GERA doubled the variance explained. A normalized risk score was associated with time-to-onset of hypertension (hazards ratio=1.18, P=10−44). Expression quantitative trait locus analysis of BP loci showed enrichment in aorta and tibial artery.