TY - JOUR
T1 - Genome-wide association analyses using electronic health records identify new loci influencing blood pressure variation
AU - Hoffmann, Thomas J.
AU - Ehret, Georg B.
AU - Nandakumar, Priyanka
AU - Ranatunga, Dilrini
AU - Schaefer, Catherine
AU - Kwok, Pui Yan
AU - Iribarren, Carlos
AU - Chakravarti, Aravinda
AU - Risch, Neil
N1 - Funding Information:
Genotyping of the GERA cohort was funded by a grant from the National Institute on Aging, National Institute of Mental Health, and National Institute of Health Common Fund (RC2 AG036607 to C.S. and N.R.). This research has been conducted using the UK Biobank Resource. This research has also been conducted using access-controlled ICBP data from dbGaP. We thank our colleagues for making these data available. Data analyses were facilitated by National Heart, Lung, and Blood Institute grant R01 HL128782 (to A.C. and N.R.).
Publisher Copyright:
© 2017 Nature America, Inc., part of Springer Nature. All rights reserved.
PY - 2017/1/1
Y1 - 2017/1/1
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/84995494168
UR - https://www.scopus.com/pages/publications/84995494168#tab=citedBy
U2 - 10.1038/ng.3715
DO - 10.1038/ng.3715
M3 - Article
C2 - 27841878
AN - SCOPUS:84995494168
SN - 1061-4036
VL - 49
SP - 54
EP - 64
JO - Nature genetics
JF - Nature genetics
IS - 1
ER -