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

Changwei Li, Yun Kyoung Kim, Rajkumar Dorajoo, Huaixing Li, I. Te Lee, Ching Yu Cheng, Meian He, Wayne H. Sheu, Xiuqing Guo, Santhi K. Ganesh, Jiang He, Juyoung Lee, Jianjun Liu, Yao Hu, Dabeeru C. Rao, Fuu Jen Tsai, Jia Yu Koh, Hua Hu, Kae Woei Liang, Walter PalmasJames E. Hixson, Sohee Han, Yik Ying Teo, Yiqin Wang, Jing Chen, Chieh Hsiang Lu, Zheng Yingfeng, Lixuan Gui, Wen Jane Lee, Jie Yao, Dongfeng Gu, Bok Ghee Han, Xueling Sim, Liang Sun, Jinying Zhao, Chien Hsiun Chen, Neelam Kumari, Yunfeng He, Kent D. Taylor, Leslie J. Raffel, Sanghoon Moon, Jerome I. Rotter, Yii Der Ida Chen, Tangchun Wu, Wong Tien Yin, Jer Yuarn Wu, Xu Lin, E. Shyong Tai, Bong Jo Kim, Tanika N. Kelly

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10 Scopus citations

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 1024.32, 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 1024.32; ATP2B1 at 1221.33; 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.

Original languageEnglish
Article numbere001527
JournalCirculation: Cardiovascular Genetics
Volume10
Issue number2
DOIs
StatePublished - Apr 1 2017
Externally publishedYes

Keywords

  • arterial pressure
  • blood pressure
  • epidemiology
  • genome-wide association study

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    Li, C., Kim, Y. K., Dorajoo, R., Li, H., Lee, I. T., Cheng, C. Y., He, M., Sheu, W. H., Guo, X., Ganesh, S. K., He, J., Lee, J., Liu, J., Hu, Y., Rao, D. C., Tsai, F. J., Koh, J. Y., Hu, H., Liang, K. W., ... Kelly, T. N. (2017). Genome-Wide Association Study Meta-Analysis of Long-Term Average Blood Pressure in East Asians. Circulation: Cardiovascular Genetics, 10(2), [e001527]. https://doi.org/10.1161/CIRCGENETICS.116.001527