Genome-Wide Association Study Meta-Analysis of Long-Term Average Blood Pressure in East Asians. (April 2017)

• Record Type: Journal Article
• Authors: Li, Changwei; Kim, Yun Kyoung; Dorajoo, Rajkumar; Li, Huaixing; Lee, I-Te; Cheng, Ching-Yu; He, Meian; Sheu, Wayne H-h; Guo, Xiuqing; Ganesh, Santhi K.; He, Jiang; Lee, Juyoung; Liu, Jianjun; Hu, Yao; Rao, Dabeeru C.; Tsai, Fuu-Jen; Koh, Jia Yu; Hu, Hua; Liang, Kae-Woei; Palmas, Walter; Hixson, James E.; Han, Sohee; Teo, Yik-Ying; Wang, Yiqin; Chen, Jing; Lu, Chieh Hsiang; Zheng, Yingfeng; Gui, Lixuan; Lee, Wen-Jane; Yao, Jie; Gu, Dongfeng; Han, Bok-Ghee; Sim, Xueling; Sun, Liang; Zhao, Jinying; Chen, Chien-Hsiun; Kumari, Neelam; He, Yunfeng; Taylor, Kent D.; Raffel, Leslie J.; Moon, Sanghoon; Rotter, Jerome I.; Ida Chen, Yii-der; Wu, Tangchun; Wong, Tien Yin; Wu, Jer-Yuarn; Lin, Xu; Tai, E-Shyong; Kim, Bong-Jo; Kelly, Tanika N.;
• Is Part Of: Circulation. Volume 10:Number 2(2017)
• Publication Date: 2017-04
• Subjects: arterial pressure -- blood pressure -- epidemiology -- genome-wide association study; Arrhythmia -- Periodicals; Heart -- Electric properties -- Periodicals; 616.1042
• DOI: 10.1161/CIRCGENETICS.116.001527
• Languages: English
• ISSNs: 1942-325X

Abstract

Abstract : 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. Abstract : Supplemental Digital Content is available in the text.