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

Publication ,  Journal Article
Li, C; Kim, YK; Dorajoo, R; Li, H; Lee, I-T; Cheng, C-Y; He, M; Sheu, WH-H; Guo, X; Ganesh, SK; He, J; Lee, J; Liu, J; Hu, Y; Rao, DC ...
Published in: Circ Cardiovasc Genet
April 2017

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.

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Published In

Circ Cardiovasc Genet

DOI

EISSN

1942-3268

Publication Date

April 2017

Volume

10

Issue

2

Start / End Page

e001527

Location

United States

Related Subject Headings

  • Polymorphism, Single Nucleotide
  • Phenotype
  • Male
  • Humans
  • Genome-Wide Association Study
  • Genetic Loci
  • Female
  • Cardiovascular System & Hematology
  • Blood Pressure
  • Asian People
 

Citation

APA
Chicago
ICMJE
MLA
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Li, C., Kim, Y. K., Dorajoo, R., Li, H., Lee, I.-T., Cheng, C.-Y., … Kelly, T. N. (2017). Genome-Wide Association Study Meta-Analysis of Long-Term Average Blood Pressure in East Asians. Circ Cardiovasc Genet, 10(2), e001527. https://doi.org/10.1161/CIRCGENETICS.116.001527
Li, Changwei, Yun Kyoung Kim, Rajkumar Dorajoo, Huaixing Li, I-Te Lee, Ching-Yu Cheng, Meian He, et al. “Genome-Wide Association Study Meta-Analysis of Long-Term Average Blood Pressure in East Asians.Circ Cardiovasc Genet 10, no. 2 (April 2017): e001527. https://doi.org/10.1161/CIRCGENETICS.116.001527.
Li C, Kim YK, Dorajoo R, Li H, Lee I-T, Cheng C-Y, et al. Genome-Wide Association Study Meta-Analysis of Long-Term Average Blood Pressure in East Asians. Circ Cardiovasc Genet. 2017 Apr;10(2):e001527.
Li, Changwei, et al. “Genome-Wide Association Study Meta-Analysis of Long-Term Average Blood Pressure in East Asians.Circ Cardiovasc Genet, vol. 10, no. 2, Apr. 2017, p. e001527. Pubmed, doi:10.1161/CIRCGENETICS.116.001527.
Li C, Kim YK, Dorajoo R, Li H, Lee I-T, Cheng C-Y, He M, Sheu WH-H, Guo X, Ganesh SK, He J, Lee J, Liu J, Hu Y, Rao DC, Tsai F-J, Koh JY, Hu H, Liang K-W, Palmas W, Hixson JE, Han S, Teo Y-Y, Wang Y, Chen J, Lu CH, Zheng Y, Gui L, Lee W-J, Yao J, Gu D, Han B-G, Sim X, Sun L, Zhao J, Chen C-H, Kumari N, He Y, Taylor KD, Raffel LJ, Moon S, Rotter JI, Ida Chen Y-D, Wu T, Wong TY, Wu J-Y, Lin X, Tai E-S, Kim B-J, Kelly TN. Genome-Wide Association Study Meta-Analysis of Long-Term Average Blood Pressure in East Asians. Circ Cardiovasc Genet. 2017 Apr;10(2):e001527.

Published In

Circ Cardiovasc Genet

DOI

EISSN

1942-3268

Publication Date

April 2017

Volume

10

Issue

2

Start / End Page

e001527

Location

United States

Related Subject Headings

  • Polymorphism, Single Nucleotide
  • Phenotype
  • Male
  • Humans
  • Genome-Wide Association Study
  • Genetic Loci
  • Female
  • Cardiovascular System & Hematology
  • Blood Pressure
  • Asian People