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

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.

SUBMITTER: Takeuchi F

PROVIDER: S-EPMC6261994 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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

Takeuchi Fumihiko F Akiyama Masato M Matoba Nana N Katsuya Tomohiro T Nakatochi Masahiro M Tabara Yasuharu Y Narita Akira A Saw Woei-Yuh WY Moon Sanghoon S Spracklen Cassandra N CN Chai Jin-Fang JF Kim Young-Jin YJ Zhang Liang L Wang Chaolong C Li Huaixing H Li Honglan H Wu Jer-Yuarn JY Dorajoo Rajkumar R Nierenberg Jovia L JL Wang Ya Xing YX He Jing J Bennett Derrick A DA Takahashi Atsushi A Momozawa Yukihide Y Hirata Makoto M Matsuda Koichi K Rakugi Hiromi H Nakashima Eitaro E Isono Masato M Shirota Matsuyuki M Hozawa Atsushi A Ichihara Sahoko S Matsubara Tatsuaki T Yamamoto Ken K Kohara Katsuhiko K Igase Michiya M Han Sohee S Gordon-Larsen Penny P Huang Wei W Lee Nanette R NR Adair Linda S LS Hwang Mi Yeong MY Lee Juyoung J Chee Miao Li ML Sabanayagam Charumathi C Zhao Wanting W Liu Jianjun J Reilly Dermot F DF Sun Liang L Huo Shaofeng S Edwards Todd L TL Long Jirong J Chang Li-Ching LC Chen Chien-Hsiun CH Yuan Jian-Min JM Koh Woon-Puay WP Friedlander Yechiel Y Kelly Tanika N TN Bin Wei Wen W Xu Liang L Cai Hui H Xiang Yong-Bing YB Lin Kuang K Clarke Robert R Walters Robin G RG Millwood Iona Y IY Li Liming L Chambers John C JC Kooner Jaspal S JS Elliott Paul P van der Harst Pim P Chen Zhengming Z Sasaki Makoto M Shu Xiao-Ou XO Jonas Jost B JB He Jiang J Heng Chew-Kiat CK Chen Yuan-Tsong YT Zheng Wei W Lin Xu X Teo Yik-Ying YY Tai E-Shyong ES Cheng Ching-Yu CY Wong Tien Yin TY Sim Xueling X Mohlke Karen L KL Yamamoto Masayuki M Kim Bong-Jo BJ Miki Tetsuro T Nabika Toru T Yokota Mitsuhiro M Kamatani Yoichiro Y Kubo Michiaki M Kato Norihiro N

Nature communications 20181128 1

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 ...[more]

PMID: 30487518

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Project description:To investigate the polygenicity of complex traits in populations of East Asian (EAS) and European (EUR) descents, we leveraged genome-wide data from Biobank Japan, UK Biobank, and FinnGen cohorts. Specifically, we analyzed up to 215 outcomes related to 18 health domains, assessing their polygenic architecture via descriptive statistics, such as the proportion of susceptibility SNPs per trait (πc). While we did not observe EAS-EUR differences in the overall distribution of polygenicity parameters across the phenotypes investigated, there were ancestry-specific patterns in the polygenicity differences between health domains. In EAS, pairwise comparisons across health domains showed enrichment for πc differences related to hematological and metabolic traits (hematological fold-enrichment = 4.45, p = 2.15 × 10-7; metabolic fold-enrichment = 4.05, p = 4.01 × 10-6). For both categories, the proportion of susceptibility SNPs was lower than that observed for several other health domains (EAS-hematological median πc = 0.15%, EAS-metabolic median πc = 0.18%) with the strongest πc difference with respect to respiratory traits (EAS-respiratory median πc = 0.50%; hematological-p = 2.26 × 10-3; metabolic-p = 3.48 × 10-3). In EUR, pairwise comparisons showed multiple πc differences related to the endocrine category (fold-enrichment = 5.83, p = 4.76 × 10-6), where these traits showed a low proportion of susceptibility SNPs (EUR-endocrine median πc = 0.01%) with the strongest difference with respect to psychiatric phenotypes (EUR-psychiatric median πc = 0.50%; p = 1.19 × 10-4). Simulating sample sizes of 1,000,000 and 5,000,000 individuals, we also showed that ancestry-specific polygenicity patterns translate into differences across health domains in the genetic variance explained by susceptibility SNPs projected to be genome-wide significant (e.g., EAS hematological-neoplasm p = 2.18 × 10-4; EUR endocrine-gastrointestinal p = 6.80 × 10-4). These findings highlight that traits related to the same health domains may present ancestry-specific variability in their polygenicity.

Dataset Information

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

Publications

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

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