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Genome-Wide Association Study Meta-Analysis of Long-Term Average Blood Pressure in East Asians.
Tuesday,2018-01-16 18:21 America/Los_Angeles — ecterry
| Title | Genome-Wide Association Study Meta-Analysis of Long-Term Average Blood Pressure in East Asians. |
| Publication Type | Journal Article |
| Year of Publication | 2017 |
| Authors | Li, C, Kim, YKyoung, 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, JYu, Hu, H, Liang, K-W, Palmas, W, Hixson, JE, Han, S, Teo, Y-Y, Wang, Y, Chen, J, Lu, CHsiang, 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, Chen, Y-DIda, Wu, T, Wong, TYin, Wu, J-Y, Lin, X, Tai, E-S, Kim, B-J, Kelly, TN |
| Journal | Circ Cardiovasc Genet |
| Volume | 10 |
| Issue | 2 |
| Pagination | e001527 |
| Date Published | 2017 Apr |
| ISSN | 1942-3268 |
| Keywords | Asian Continental Ancestry Group, Blood Pressure, Far East, Female, Genetic Loci, Genome-Wide Association Study, Humans, Male, Phenotype, Polymorphism, Single Nucleotide |
| Abstract | <p><b>BACKGROUND: </b>Genome-wide single marker and gene-based meta-analyses of long-term average (LTA) blood pressure (BP) phenotypes may reveal novel findings for BP.</p><p><b>METHODS AND RESULTS: </b>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).</p><p><b>CONCLUSIONS: </b>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.</p> |
| DOI | 10.1161/CIRCGENETICS.116.001527 |
| Alternate Journal | Circ Cardiovasc Genet |
| PubMed ID | 28348047 |
| PubMed Central ID | PMC5704911 |
| Grant List | HHSN268201100012C / HL / NHLBI NIH HHS / United States N01 HC085086 / HC / NHLBI NIH HHS / United States HHSN268201300026C / HL / NHLBI NIH HHS / United States N01 AG012100 / AG / NIA NIH HHS / United States N01 HC085081 / HC / NHLBI NIH HHS / United States HHSN268201100010C / HL / NHLBI NIH HHS / United States UL1 RR025005 / RR / NCRR NIH HHS / United States N01 HC095167 / HC / NHLBI NIH HHS / United States HHSN268201100008C / HL / NHLBI NIH HHS / United States UL1 TR001079 / TR / NCATS NIH HHS / United States R01 HL043851 / HL / NHLBI NIH HHS / United States R01 HL059367 / HL / NHLBI NIH HHS / United States HHSN268201100007C / HL / NHLBI NIH HHS / United States HHSN268200800007C / HL / NHLBI NIH HHS / United States N01 HC085083 / HC / NHLBI NIH HHS / United States N01 HC025195 / HC / NHLBI NIH HHS / United States N01 HC095161 / HC / NHLBI NIH HHS / United States HHSN268201100011C / HL / NHLBI NIH HHS / United States R01 HL086694 / HL / NHLBI NIH HHS / United States UL1 RR024156 / RR / NCRR NIH HHS / United States N02 HL64278 / HL / NHLBI NIH HHS / United States N01 HC095164 / HC / NHLBI NIH HHS / United States R01 HL087652 / HL / NHLBI NIH HHS / United States N01 HC095166 / HC / NHLBI NIH HHS / United States U01 HG004402 / HG / NHGRI NIH HHS / United States UL1 TR000124 / TR / NCATS NIH HHS / United States HHSN268201300025C / HL / NHLBI NIH HHS / United States N01 HC095160 / HC / NHLBI NIH HHS / United States N01HC55222 / HL / NHLBI NIH HHS / United States R01 HL105756 / HL / NHLBI NIH HHS / United States N01 HC085082 / HC / NHLBI NIH HHS / United States U01 HG004729 / HG / NHGRI NIH HHS / United States P30 DK063491 / DK / NIDDK NIH HHS / United States N01 HC085080 / HC / NHLBI NIH HHS / United States HHSN268201300027C / HL / NHLBI NIH HHS / United States HHSN268201100006C / HL / NHLBI NIH HHS / United States HHSN268201200036C / HL / NHLBI NIH HHS / United States R01 EY014684 / EY / NEI NIH HHS / United States HHSN268200900041C / HL / NHLBI NIH HHS / United States HHSN268201300028C / HL / NHLBI NIH HHS / United States R01 HL084099 / HL / NHLBI NIH HHS / United States N01 HC095169 / HC / NHLBI NIH HHS / United States R01 HL080295 / HL / NHLBI NIH HHS / United States N01 HC095165 / HC / NHLBI NIH HHS / United States R01 HL087263 / HL / NHLBI NIH HHS / United States U01 HL072507 / HL / NHLBI NIH HHS / United States HHSN268201100009C / HL / NHLBI NIH HHS / United States HHSN268201100005C / HL / NHLBI NIH HHS / United States N01 HC095168 / HC / NHLBI NIH HHS / United States UL1 TR000040 / TR / NCATS NIH HHS / United States N01 HC095163 / HC / NHLBI NIH HHS / United States N01HC85079 / HL / NHLBI NIH HHS / United States HHSN268201300029C / HL / NHLBI NIH HHS / United States R01 AG023629 / AG / NIA NIH HHS / United States R01 HL087641 / HL / NHLBI NIH HHS / United States R01 HL090682 / HL / NHLBI NIH HHS / United States N01 HC095162 / HC / NHLBI NIH HHS / United States N01 HC095159 / HC / NHLBI NIH HHS / United States |
ePub date:
17/04