Genome-Wide Association Study Meta-Analysis of Long-Term Average Blood Pressure in East Asians

초록

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 18422 East Asian participants (stage 1) followed by replication study of <= 46629 participants of European ancestry (stage 2). Significant single-nucleotide polymorphisms and genes were determined by a P<5.0x10(-8) and 2.5x10(-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=5.03x10(-8), stage-2 P=8.64x10(-3), joint P=2.63x10(-8)) and mean arterial pressure (stage-1 P=3.59x10(-9), stage-2 P=2.35x10(-2), joint P=2.64x10(-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=8.55x10(-6), stage-2 P=1.62x10(-5), joint P=3.28x10(-9)) and mean arterial pressure (stage-1 P=9.19x10(-7), stage-2 P=9.69x10(-5), joint P=2.15x10(-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=1.27x10(-4) and 3.30x10(-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.

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