Genome-wide association study meta-analysis reveals transethnic replication of mean arterial and pulse pressure loci

Tanika N. Kelly, Fumihiko Takeuchi, Yasuharu Tabara, Todd L. Edwards, Young Jin Kim, Peng Chen, Huaixing Li, Ying Wu, Chi Fan Yang, Yonghong Zhang, Dongfeng Gu, Tomohiro Katsuya, Takayoshi Ohkubo, Yu Tang Gao, Min Jin Go, Yik Ying Teo, Ling Lu, Nanette R. Lee, Li Ching Chang, Hao PengQi Zhao, Eitaro Nakashima, Yoshikuni Kita, Xiao Ou Shu, Nam Hee Kim, E. Shyong Tai, Yiqin Wang, Linda S. Adair, Chien Hsiun Chen, Shihiu Zhang, Changwei Li, Toru Nabika, Satoshi Umemura, Qiuyin Cai, Yoon Shin Cho, Tien Yin Wong, Jingwen Zhu, Jer Yuarn Wu, Xin Gao, James E. Hixson, Hui Cai, Juyoung Lee, Ching Yu Cheng, Dabeeru C. Rao, Yong Bing Xiang, Myeong Chan Cho, Bok Ghee Han, Aili Wang, Fuu Jen Tsai, Karen Mohlke, Xu Lin, Mohammad Kamran Ikram, Jong Young Lee, Wei Zheng, Miki Tetsuro, Norihiro Kato, Jiang He

Research output: Contribution to journalArticlepeer-review

56 Scopus citations

Abstract

We conducted a genome-wide association study meta-analysis of mean arterial pressure and pulse pressure among 26 600 East Asian participants (stage 1) followed by replication study of up to 28 783 participants (stage 2). For novel loci, statistical significance was determined by a P<5.0×10 in joint analysis of stage 1 and stage 2 data. For loci reported by the previous mean arterial and pulse pressure genome-wide association study meta-analysis in Europeans, evidence of transethnic replication was determined by consistency in effect direction and a Bonferroni-corrected P<1.4×10. No novel loci were identified by the current study. Five independent mean arterial pressure variants demonstrated robust evidence for transethnic replication including rs17249754 at ATP2B1 (P=7.5×10), rs2681492 at ATP2B1 (P=3.4×10), rs11191593 at NT5C2 (1.1×10), rs3824755 at CYP17A1 (P=1.2×10), and rs13149993 at FGF5 (P=2.4×10). Two additional variants showed suggestive evidence of transethnic replication (consistency in effect direction and P<0.05), including rs319690 at MAP4 (P=0.014) and rs1173771 at NPR3 (P=0.018). For pulse pressure, robust evidence of replication was identified for 2 independent variants, including rs17249754 at ATP2B1 (P=1.2×10) and rs11191593 at NT5C2 (P=1.1×10), with suggestive evidence of replication among an additional 2 variants including rs3824755 at CYP17A1 (P=6.1×10) and rs2681492 at ATP2B1 (P=9.0×10). Replicated variants demonstrated consistency in effect sizes between East Asian and European samples, with effect size differences ranging from 0.03 to 0.24 mm Hg for mean arterial pressure and from 0.03 to 0.21 mm Hg for pulse pressure. In conclusion, we present the first evidence of transethnic replication of several mean arterial and pulse pressure loci in an East Asian population.

Original languageEnglish
Pages (from-to)853-859
Number of pages7
JournalHypertension
Volume62
Issue number5
DOIs
StatePublished - Nov 2013

Keywords

  • blood pressure
  • genetics
  • genome-wide association study
  • hypertension
  • meta-analysis
  • polymorphism single nucleotide

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