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

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 <5.0×10 and 2.5×10, respectively, in joint analyses of stage-1 and stage-2 data. We identified 1 novel variant, rs4919669 at 10q24.32, influencing LTA systolic BP (stage-1 =5.03×10, stage-2 =8.64×10, joint =2.63×10) and mean arterial pressure (stage-1 =3.59×10, stage-2 =2.35×10, joint =2.64×10). Three previously reported BP loci (, , and ) were also identified for all BP phenotypes. Gene-based analysis provided the first robust evidence for association of with LTA systolic BP (stage-1 =8.55×10, stage-2 =1.62×10, joint =3.28×10) and mean arterial pressure (stage-1 =9.19×10, stage-2 =9.69×10, joint =2.15×10) phenotypes. Fourteen genes (, , , , , , , , -, , , and at 10q24.32; at 12q21.33; and 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 marker rs1275988 at 2p23.3 with LTA systolic BP and mean arterial pressure phenotypes (=1.27×10 and 3.30×10, respectively).

CONCLUSIONS: We identified 1 novel variant and 1 novel gene and present the first direct evidence of relevance of the locus for LTA BP among East Asians.