Interethnic analyses of blood pressure loci in populations of East Asian and European descent.pdf (1.9 MB)
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Interethnic analyses of blood pressure loci in populations of East Asian and European descent.

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journal contribution
posted on 15.08.2019, 11:41 by F Takeuchi, M Akiyama, N Matoba, T Katsuya, M Nakatochi, Y Tabara, A Narita, W-Y Saw, S Moon, CN Spracklen, J-F Chai, Y-J Kim, L Zhang, C Wang, H Li, J-Y Wu, R Dorajoo, JL Nierenberg, YX Wang, J He, DA Bennett, A Takahashi, Y Momozawa, M Hirata, K Matsuda, H Rakugi, E Nakashima, M Isono, M Shirota, A Hozawa, S Ichihara, T Matsubara, K Yamamoto, K Kohara, M Igase, S Han, P Gordon-Larsen, W Huang, NR Lee, LS Adair, MY Hwang, J Lee, ML Chee, C Sabanayagam, W Zhao, J Liu, DF Reilly, L Sun, S Huo, TL Edwards, J Long, L-C Chang, C-H Chen, J-M Yuan, W-P Koh, Y Friedlander, TN Kelly, W Bin Wei, L Xu, H Cai, Y-B Xiang, K Lin, R Clarke, RG Walters, IY Millwood, L Li, JC Chambers, JS Kooner, P Elliott, P van der Harst, International Genomics of Blood Pressure (iGEN-BP) Consortium, Z Chen, M Sasaki, X-O Shu, JB Jonas, C-K Heng, Y-T Chen, W Zheng, X Lin, Y-Y Teo, E-S Tai, C-Y Cheng, TY Wong, X Sim, KL Mohlke, M Yamamoto, B-J Kim, T Miki, T Nabika, M Yokota, Y Kamatani, M Kubo, N Kato
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.

Funding

We acknowledge the use of data from the International Consortium for Blood Pressure Genome-Wide Association Studies 3 and the AGEN-height Consortium 42. This research has been conducted using the UK Biobank Resource 14. Additional acknowledgements can be found in Supplementary Note 1.

History

Citation

Nature Communications, 2018, 9:5052

Author affiliation

/Organisation/COLLEGE OF LIFE SCIENCES/School of Medicine/Department of Cardiovascular Sciences

Version

VoR (Version of Record)

Published in

Nature Communications

Publisher

Nature Research (part of Springer Nature)

eissn

2041-1723

Acceptance date

29/10/2018

Copyright date

2018

Available date

15/08/2019

Publisher version

https://www.nature.com/articles/s41467-018-07345-0

Notes

Supplementary Information accompanies this paper at https://doi.org/10.1038/s41467-018-07345-0 Full summary statistics relating to the GWAS meta-analysis has been deposited at the European Genome-phenome Archive (EGA), which is hosted by the EBI and the CRG, under accession number EGAS00001002991. Further information about EGA can be found on https://ega-archive.org “The European Genome-phenome Archive of human data consented for biomedical research” (http://www.nature.com/ng/journal/v47/n7/full/ng.3312.html). All relevant data are available from the authors.

Language

en