1. Genome-Wide Association Study Meta-Analysis of Long-Term Average Blood Pressure in East Asians.
- Author
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Li C, Kim YK, Dorajoo R, Li H, Lee IT, Cheng CY, He M, Sheu WH, Guo X, Ganesh SK, He J, Lee J, Liu J, Hu Y, Rao DC, Tsai FJ, Koh JY, Hu H, Liang KW, Palmas W, Hixson JE, Han S, Teo YY, Wang Y, Chen J, Lu CH, Zheng Y, Gui L, Lee WJ, Yao J, Gu D, Han BG, Sim X, Sun L, Zhao J, Chen CH, Kumari N, He Y, Taylor KD, Raffel LJ, Moon S, Rotter JI, Ida Chen YD, Wu T, Wong TY, Wu JY, Lin X, Tai ES, Kim BJ, and Kelly TN
- Subjects
- Asia, Eastern, Female, Humans, Male, Asian People genetics, Blood Pressure genetics, Genetic Loci, Genome-Wide Association Study, Phenotype, Polymorphism, Single Nucleotide
- 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., (© 2017 American Heart Association, Inc.)- Published
- 2017
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