04127nas a2200853 4500008004100000022001400041245010000055210006900155260001300224300001200237490000700249520188400256653003702140653001902177653001302196653001102209653001702220653003402237653001102271653000902282653001402291653003602305100001702341700002102358700002202379700001702401700001402418700002002432700001402452700002102466700001702487700002202504700001402526700001702540700001702557700001202574700002002586700001802606700001702624700001202641700002002653700001902673700002102692700001502713700001802728700001602746700001502762700002202777700002002799700001602819700001802835700001302853700001702866700001802883700001702901700001502918700001802933700002202951700001902973700001602992700002003008700002203028700001903050700002203069700002303091700001703114700002003131700001803151700001203169700001803181700001703199700002103216856003603237 2017 eng d a1942-326800aGenome-Wide Association Study Meta-Analysis of Long-Term Average Blood Pressure in East Asians.0 aGenomeWide Association Study MetaAnalysis of LongTerm Average Bl c2017 Apr ae0015270 v103 a
BACKGROUND: Genome-wide single marker and gene-based meta-analyses of long-term average (LTA) blood pressure (BP) phenotypes may reveal novel findings for BP.
METHODS AND RESULTS: We conducted genome-wide analysis among 18 422 East Asian participants (stage 1) followed by replication study of ≤46 629 participants of European ancestry (stage 2). Significant single-nucleotide polymorphisms and genes were determined by a P<5.0×10-8 and 2.5×10-6, respectively, in joint analyses of stage-1 and stage-2 data. We identified 1 novel ARL3 variant, rs4919669 at 10q24.32, influencing LTA systolic BP (stage-1 P=5.03×10-8, stage-2 P=8.64×10-3, joint P=2.63×10-8) and mean arterial pressure (stage-1 P=3.59×10-9, stage-2 P=2.35×10-2, joint P=2.64×10-8). Three previously reported BP loci (WBP1L, NT5C2, and ATP2B1) were also identified for all BP phenotypes. Gene-based analysis provided the first robust evidence for association of KCNJ11 with LTA systolic BP (stage-1 P=8.55×10-6, stage-2 P=1.62×10-5, joint P=3.28×10-9) and mean arterial pressure (stage-1 P=9.19×10-7, stage-2 P=9.69×10-5, joint P=2.15×10-9) phenotypes. Fourteen genes (TMEM180, ACTR1A, SUFU, ARL3, SFXN2, WBP1L, CYP17A1, C10orf32, C10orf32-ASMT, AS3MT, CNNM2, and NT5C2 at 10q24.32; ATP2B1 at 12q21.33; and NCR3LG1 at 11p15.1) implicated by previous genome-wide association study meta-analyses were also identified. Among the loci identified by the previous genome-wide association study meta-analysis of LTA BP, we transethnically replicated associations of the KCNK3 marker rs1275988 at 2p23.3 with LTA systolic BP and mean arterial pressure phenotypes (P=1.27×10-4 and 3.30×10-4, respectively).
CONCLUSIONS: We identified 1 novel variant and 1 novel gene and present the first direct evidence of relevance of the KCNK3 locus for LTA BP among East Asians.
10aAsian Continental Ancestry Group10aBlood Pressure10aFar East10aFemale10aGenetic Loci10aGenome-Wide Association Study10aHumans10aMale10aPhenotype10aPolymorphism, Single Nucleotide1 aLi, Changwei1 aKim, Yun, Kyoung1 aDorajoo, Rajkumar1 aLi, Huaixing1 aLee, I-Te1 aCheng, Ching-Yu1 aHe, Meian1 aSheu, Wayne, H-H1 aGuo, Xiuqing1 aGanesh, Santhi, K1 aHe, Jiang1 aLee, Juyoung1 aLiu, Jianjun1 aHu, Yao1 aRao, Dabeeru, C1 aTsai, Fuu-Jen1 aKoh, Jia, Yu1 aHu, Hua1 aLiang, Kae-Woei1 aPalmas, Walter1 aHixson, James, E1 aHan, Sohee1 aTeo, Yik-Ying1 aWang, Yiqin1 aChen, Jing1 aLu, Chieh, Hsiang1 aZheng, Yingfeng1 aGui, Lixuan1 aLee, Wen-Jane1 aYao, Jie1 aGu, Dongfeng1 aHan, Bok-Ghee1 aSim, Xueling1 aSun, Liang1 aZhao, Jinying1 aChen, Chien-Hsiun1 aKumari, Neelam1 aHe, Yunfeng1 aTaylor, Kent, D1 aRaffel, Leslie, J1 aMoon, Sanghoon1 aRotter, Jerome, I1 aChen, Yii-Der, Ida1 aWu, Tangchun1 aWong, Tien, Yin1 aWu, Jer-Yuarn1 aLin, Xu1 aTai, E-Shyong1 aKim, Bong-Jo1 aKelly, Tanika, N uhttps://chs-nhlbi.org/node/7571