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Y Okada X Sim MJ Go JY Wu D Gu F Takeuchi A Takahashi S Maeda T Tsunoda P Chen SC Lim TY Wong J Liu TL Young T Aung M Seielstad YY Teo YJ Kim JY Lee BG Han D Kang CH Chen FJ Tsai LC Chang SJ Fann H Mei DC Rao JE Hixson S Chen T Katsuya M Isono T Ogihara JC Chambers W Zhang JS Kooner;KidneyGen Consortium;CKDGen Consortium E Albrecht;GUGC consortium K Yamamoto M Kubo Y Nakamura N Kamatani N Kato J He YT Chen YS Cho ES Tai T Tanaka 《Nature genetics》2012,44(8):904-909
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. 相似文献
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Kooner JS Saleheen D Sim X Sehmi J Zhang W Frossard P Been LF Chia KS Dimas AS Hassanali N Jafar T Jowett JB Li X Radha V Rees SD Takeuchi F Young R Aung T Basit A Chidambaram M Das D Grundberg E Hedman AK Hydrie ZI Islam M Khor CC Kowlessur S Kristensen MM Liju S Lim WY Matthews DR Liu J Morris AP Nica AC Pinidiyapathirage JM Prokopenko I Rasheed A Samuel M Shah N Shera AS Small KS Suo C Wickremasinghe AR Wong TY Yang M Zhang F;DIAGRAM;MuTHER Abecasis GR Barnett AH Caulfield M Deloukas P 《Nature genetics》2011,43(10):984-989
We carried out a genome-wide association study of type-2 diabetes (T2D) in individuals of South Asian ancestry. Our discovery set included 5,561 individuals with T2D (cases) and 14,458 controls drawn from studies in London, Pakistan and Singapore. We identified 20 independent SNPs associated with T2D at P < 10(-4) for testing in a replication sample of 13,170 cases and 25,398 controls, also all of South Asian ancestry. In the combined analysis, we identified common genetic variants at six loci (GRB14, ST6GAL1, VPS26A, HMG20A, AP3S2 and HNF4A) newly associated with T2D (P = 4.1 × 10(-8) to P = 1.9 × 10(-11)). SNPs at GRB14 were also associated with insulin sensitivity (P = 5.0 × 10(-4)), and SNPs at ST6GAL1 and HNF4A were also associated with pancreatic beta-cell function (P = 0.02 and P = 0.001, respectively). Our findings provide additional insight into mechanisms underlying T2D and show the potential for new discovery from genetic association studies in South Asians, a population with increased susceptibility to T2D. 相似文献
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Chambers JC Elliott P Zabaneh D Zhang W Li Y Froguel P Balding D Scott J Kooner JS 《Nature genetics》2008,40(6):716-718
We carried out a genome-wide association study (318,237 SNPs) for insulin resistance and related phenotypes in 2,684 Indian Asians, with further testing in 11,955 individuals of Indian Asian or European ancestry. We found associations of rs12970134 near MC4R with waist circumference (P = 1.7 x 10(-9)) and, independently, with insulin resistance. Homozygotes for the risk allele of rs12970134 have approximately 2 cm increased waist circumference. Common genetic variation near MC4R is associated with risk of adiposity and insulin resistance. 相似文献
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