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

Hoffmann, Thomas J
Nandakumar, Priyanka
Ranatunga, Dilrini
Schaefer, Catherine
Kwok, Pui-Yan
Iribarren, Carlos
Chakravarti, Aravinda
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Published in Nature Genetics. 2017, vol. 49, no. 1, p. 54-64
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 AdultBlood Pressure/geneticsCohort StudiesElectronic Health RecordsEthnic Groups/geneticsFemaleGenetic Loci/geneticsGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansHypertension/epidemiology/geneticsLongitudinal StudiesMaleMeta-Analysis as TopicMiddle AgedPhenotypePolymorphismSingle Nucleotide/geneticsPrevalence
PMID: 27841878
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Research group Traits génétiques complexes (901)
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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 https://archive-ouverte.unige.ch/unige:128769

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Deposited on : 2020-01-13

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