title: 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 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.
authors.affiliation: Department of Epidemiology and Biostatistics, University of California at San Francisco, San Francisco, California, USA.|Institute for Human Genetics, University of California at San Francisco, San Francisco, California, USA.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Hoffmann
authors.affiliation: Center for Complex Disease Genomics, McKusick-Nathans Institute of Genetic Medicine, Baltimore, Maryland, USA.|Cardiology, Department of Specialties of Internal Medicine, University of Geneva, Geneva, Switzerland.
authors.forename: Georg B
authors.identifier: 0000-0002-5730-0675
authors.initials: GB
authors.lastname: Ehret
authors.affiliation: Center for Complex Disease Genomics, McKusick-Nathans Institute of Genetic Medicine, Baltimore, Maryland, USA.
authors.forename: Priyanka
authors.initials: P
authors.lastname: Nandakumar
authors.affiliation: Kaiser Permanente Northern California Division of Research, Oakland, California, USA.
authors.forename: Dilrini
authors.initials: D
authors.lastname: Ranatunga
authors.affiliation: Kaiser Permanente Northern California Division of Research, Oakland, California, USA.
authors.forename: Catherine
authors.initials: C
authors.lastname: Schaefer
authors.affiliation: Institute for Human Genetics, University of California at San Francisco, San Francisco, California, USA.
authors.forename: Pui-Yan
authors.initials: PY
authors.lastname: Kwok
authors.affiliation: Kaiser Permanente Northern California Division of Research, Oakland, California, USA.
authors.forename: Carlos
authors.initials: C
authors.lastname: Iribarren
authors.affiliation: Center for Complex Disease Genomics, McKusick-Nathans Institute of Genetic Medicine, Baltimore, Maryland, USA.
authors.forename: Aravinda
authors.initials: A
authors.lastname: Chakravarti
authors.affiliation: Department of Epidemiology and Biostatistics, University of California at San Francisco, San Francisco, California, USA.|Institute for Human Genetics, University of California at San Francisco, San Francisco, California, USA.|Kaiser Permanente Northern California Division of Research, Oakland, California, USA.
authors.forename: Neil
authors.initials: N
authors.lastname: Risch
mesh_terms: D000328:Adult; D001794:Blood Pressure / Q000235:genetics*; D015331:Cohort Studies; D057286:Electronic Health Records; D005006:Ethnicity / Q000235:genetics; D005260:Female; D056426:Genetic Loci / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D006973:Hypertension / Q000453:epidemiology / Q000235:genetics*; D008137:Longitudinal Studies; D008297:Male; D015201:Meta-Analysis as Topic; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D015995:Prevalence