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Meta-analysis identifies multiple loci associated with kidney function-related traits in east Asian populations.

ABSTRACT: Chronic kidney disease (CKD), impairment of kidney function, is a serious public health problem, and the assessment of genetic factors influencing kidney function has substantial clinical relevance. Here, we report a meta-analysis of genome-wide association studies for kidney function-related traits, including 71,149 east Asian individuals from 18 studies in 11 population-, hospital- or family-based cohorts, conducted as part of the Asian Genetic Epidemiology Network (AGEN). Our meta-analysis identified 17 loci newly associated with kidney function-related traits, including the concentrations of blood urea nitrogen, uric acid and serum creatinine and estimated glomerular filtration rate based on serum creatinine levels (eGFRcrea) (P < 5.0 × 10(-8)). We further examined these loci with in silico replication in individuals of European ancestry from the KidneyGen, CKDGen and GUGC consortia, including a combined total of ?110,347 individuals. We identify pleiotropic associations among these loci with kidney function-related traits and risk of CKD. These findings provide new insights into the genetics of kidney function.

SUBMITTER: Okada Y

PROVIDER: S-EPMC4737645 | biostudies-literature | 2012 Jul

REPOSITORIES: biostudies-literature

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Meta-analysis identifies multiple loci associated with kidney function-related traits in east Asian populations.

Okada Yukinori Y Sim Xueling X Go Min Jin MJ Wu Jer-Yuarn JY Gu Dongfeng D Takeuchi Fumihiko F Takahashi Atsushi A Maeda Shiro S Tsunoda Tatsuhiko T Chen Peng P Lim Su-Chi SC Wong Tien-Yin TY Liu Jianjun J Young Terri L TL Aung Tin T Seielstad Mark M Teo Yik-Ying YY Kim Young Jin YJ Lee Jong-Young JY Han Bok-Ghee BG Kang Daehee D Chen Chien-Hsiun CH Tsai Fuu-Jen FJ Chang Li-Ching LC Fann S-J Cathy SJ Mei Hao H Rao Dabeeru C DC Hixson James E JE Chen Shufeng S Katsuya Tomohiro T Isono Masato M Ogihara Toshio T Chambers John C JC Zhang Weihua W Kooner Jaspal S JS Albrecht Eva E Yamamoto Kazuhiko K Kubo Michiaki M Nakamura Yusuke Y Kamatani Naoyuki N Kato Norihiro N He Jiang J Chen Yuan-Tsong YT Cho Yoon Shin YS Tai E-Shyong ES Tanaka Toshihiro T

Nature genetics 20120715 8

Chronic kidney disease (CKD), impairment of kidney function, is a serious public health problem, and the assessment of genetic factors influencing kidney function has substantial clinical relevance. Here, we report a meta-analysis of genome-wide association studies for kidney function-related traits, including 71,149 east Asian individuals from 18 studies in 11 population-, hospital- or family-based cohorts, conducted as part of the Asian Genetic Epidemiology Network (AGEN). Our meta-analysis id ...[more]

PMID: 22797727

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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

Meta-analysis identifies multiple loci associated with kidney function-related traits in east Asian populations.

Publications

Meta-analysis identifies multiple loci associated with kidney function-related traits in east Asian populations.

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