Scientific article
English

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

Published inNature Genetics, vol. 49, no. 1, p. 54-64
Publication date2017
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 new loci among 75 genome-wide significant loci (P ≤ 5 × 10-8), with 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 new loci, with most replicating in UKB. Combining all three studies (n = 321,262) yielded 241 additional genome-wide significant loci, although no replication sample was available for these. All associated loci explained 2.9%, 2.5%, and 3.1% of variation in systolic, diastolic, and pulse pressure, respectively, in GERA non-Hispanic whites. Using multiple blood pressure measurements in GERA doubled the variance explained. A normalized risk score was associated with time to onset of hypertension (hazards ratio = 1.18, P = 8.2 × 10-45). Expression quantitative trait locus analysis of blood pressure loci showed enrichment in aorta and tibial artery.

Keywords
  • Adult
  • Blood Pressure/genetics
  • Cohort Studies
  • Electronic Health Records
  • Ethnic Groups/genetics
  • Female
  • Genetic Loci/genetics
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • Humans
  • Hypertension/epidemiology/genetics
  • Longitudinal Studies
  • Male
  • Meta-Analysis as Topic
  • Middle Aged
  • Phenotype
  • Polymorphism
  • Single Nucleotide/genetics
  • Prevalence
Research groups
Citation (ISO format)
HOFFMANN, Thomas J et al. Genome-wide association analyses using electronic health records identify new loci influencing blood pressure variation. In: Nature Genetics, 2017, vol. 49, n° 1, p. 54–64. doi: 10.1038/ng.3715
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Article (Published version)
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Identifiers
Journal ISSN1061-4036
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