期刊
NATURE GENETICS
卷 49, 期 1, 页码 54-64出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ng.3715
关键词
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资金
- National Institute on Aging
- National Institute of Mental Health
- National Institute of Health Common Fund [RC2 AG036607]
- National Heart, Lung, and Blood Institute [R01 HL128782]
- Geneva University Hospitals
- Foundation of Medical Researchers, Geneva
- Medical Research Council [MC_qA137853] Funding Source: researchfish
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 x 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 x 10(-45)). Expression quantitative trait locus analysis of blood pressure loci showed enrichment in aorta and tibial artery.
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