%0 Journal Article %J Circ Cardiovasc Genet %D 2017 %T Genome-Wide Association Study Meta-Analysis of Long-Term Average Blood Pressure in East Asians. %A Li, Changwei %A Kim, Yun Kyoung %A Dorajoo, Rajkumar %A Li, Huaixing %A Lee, I-Te %A Cheng, Ching-Yu %A He, Meian %A Sheu, Wayne H-H %A Guo, Xiuqing %A Ganesh, Santhi K %A He, Jiang %A Lee, Juyoung %A Liu, Jianjun %A Hu, Yao %A Rao, Dabeeru C %A Tsai, Fuu-Jen %A Koh, Jia Yu %A Hu, Hua %A Liang, Kae-Woei %A Palmas, Walter %A Hixson, James E %A Han, Sohee %A Teo, Yik-Ying %A Wang, Yiqin %A Chen, Jing %A Lu, Chieh Hsiang %A Zheng, Yingfeng %A Gui, Lixuan %A Lee, Wen-Jane %A Yao, Jie %A Gu, Dongfeng %A Han, Bok-Ghee %A Sim, Xueling %A Sun, Liang %A Zhao, Jinying %A Chen, Chien-Hsiun %A Kumari, Neelam %A He, Yunfeng %A Taylor, Kent D %A Raffel, Leslie J %A Moon, Sanghoon %A Rotter, Jerome I %A Ida Chen, Yii-Der %A Wu, Tangchun %A Wong, Tien Yin %A Wu, Jer-Yuarn %A Lin, Xu %A Tai, E-Shyong %A Kim, Bong-Jo %A Kelly, Tanika N %K Asian Continental Ancestry Group %K Blood Pressure %K Far East %K Female %K Genetic Loci %K Genome-Wide Association Study %K Humans %K Male %K Phenotype %K Polymorphism, Single Nucleotide %X

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.

%B Circ Cardiovasc Genet %V 10 %P e001527 %8 2017 Apr %G eng %N 2 %R 10.1161/CIRCGENETICS.116.001527