Interethnic analyses of blood pressure loci in populations of East Asian and European descent

Fumihiko Takeuchi, Masato Akiyama, Nana Matoba, Tomohiro Katsuya, Masahiro Nakatochi*, Yasuharu Tabara, Akira Narita, Woei-Yuh Saw, Sanghoon Moon, Cassandra N. Spracklen, Jin-Fang Chai, Young-Jin Kim, Liang Zhang, Chaolong Wang, Huaixing Li, Honglan Li, Jer-Yuarn Wu, Rajkumar Dorajoo, Jovia L. Nierenberg, Ya Xing WangJing He, Derrick A. Bennett, Atsushi Takahashi, Yukihide Momozawa, Makoto Hirata, Koichi Matsuda, Hiromi Rakugi, Eitaro Nakashima, Masato Isono, Matsuyuki Shirota, Atsushi Hozawa, Sahoko Ichihara, Tatsuaki Matsubara, Ken Yamamoto, Katsuhiko Kohara, Michiya Igase, Sohee Han, Penny Gordon-Larsen, Wei Huang, Nanette R. Lee, Linda S. Adair, Mi Yeong Hwang, Juyoung Lee, Miao Li Chee, Charumathi Sabanayagam, Wanting Zhao, Jianjun Liu, Dermot F. Reilly, Liang Sun, Shaofeng Huo, Joseph Kleinjans, International Genomics of Blood Pressure (iGEN-BP) Consortium

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Blood pressure (BP) is a major risk factor for cardiovascular disease and more than 200 genetic loci associated with BP are known. Here, we perform a multi-stage genome-wide association study for BP ( max N = 289,038) principally in East Asians and meta-analysis in East Asians and Europeans. We report 19 new genetic loci and ancestry-specific BP variants, conforming to a common ancestry-specific variant association model. At 10 unique loci, distinct non-rare ancestry-specific variants colocalize within the same linkage disequilibrium block despite the significantly discordant effects for the proxy shared variants between the ethnic groups. The genome-wide transethnic correlation of causal-variant effect-sizes is 0.898 and 0.851 for systolic and diastolic BP, respectively. Some of the ancestry-specific association signals are also influenced by a selective sweep. Our results provide new evidence for the role of common ancestry-specific variants and natural selection in ethnic differences in complex traits such as BP.

Original languageEnglish
Article number5052
Pages (from-to)1-16
Number of pages16
JournalNature Communications
Volume9
DOIs
Publication statusPublished - 28 Nov 2018

Keywords

  • GENOME-WIDE ASSOCIATION
  • BODY-MASS INDEX
  • LINKAGE DISEQUILIBRIUM
  • CARDIOVASCULAR-DISEASE
  • FUNCTIONAL ANNOTATION
  • RARE VARIANTS
  • COMMON
  • METAANALYSIS
  • HERITABILITY
  • ARCHITECTURE

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