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 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.
(© 2017 American Heart Association, Inc.)