Genome-Wide Association Study Meta-Analysis of Long-Term Average Blood Pressure in East Asians.
(Journal Article;Multicenter Study)
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.
Li, C; Kim, YK; Dorajoo, R; Li, H; Lee, I-T; Cheng, C-Y; He, M; Sheu, WH-H; Guo, X; Ganesh, SK; He, J; Lee, J; Liu, J; Hu, Y; Rao, DC; Tsai, F-J; Koh, JY; Hu, H; Liang, K-W; Palmas, W; Hixson, JE; Han, S; Teo, Y-Y; Wang, Y; Chen, J; Lu, CH; Zheng, Y; Gui, L; Lee, W-J; Yao, J; Gu, D; Han, B-G; Sim, X; Sun, L; Zhao, J; Chen, C-H; Kumari, N; He, Y; Taylor, KD; Raffel, LJ; Moon, S; Rotter, JI; Ida Chen, Y-D; Wu, T; Wong, TY; Wu, J-Y; Lin, X; Tai, E-S; Kim, B-J; Kelly, TN
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