期刊
DIABETES
卷 61, 期 8, 页码 2187-2194出版社
AMER DIABETES ASSOC
DOI: 10.2337/db11-0751
关键词
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资金
- National Institutes of Health National Institute of Diabetes and Digestive and Kidney Diseases Grant [R01-DK-081923]
- Science Foundation Ireland U.S.-Ireland RD partnership
- Health Research Board Ireland
- Juvenile Diabetes Research Foundation postdoctoral fellowship [3-2011-70]
- Folkhalsan Research Foundation
- Wilhelm and Else Stockmann Foundation
- Livoch Halsa Foundation
- Helsinki University Central Hospital Research Funds
- Sigrid Juselius Foundation
- Signe and Arne Gyllenberg Foundation
- Finska Lakaresallskapet
- European Commission
- European Union's Seventh Framework Program [IMI/115006]
- Medical Research Council [MR/K003364/1] Funding Source: researchfish
- Public Health Agency [STL/3714/07] Funding Source: researchfish
We formed the GEnetics of Nephropathy-an International Effort (GENIE) consortium to examine previously reported genetic associations with diabetic nephropathy (DN) in type 1 diabetes. GENIE consists of 6,366 similarly ascertained participants of European ancestry with type 1 diabetes, with and without DN, from the All Ireland-Warren 3-Genetics of Kidneys in Diabetes U.K. and Republic of Ireland (U.K.-R.O.I.) collection and the Finnish Diabetic Nephropathy Study (FinnDiane), combined with reanalyzed data from the Genetics of Kidneys in Diabetes U.S. Study (U.S. GoKinD). We found little evidence for the association of the EPO promoter polymorphism, rs161740, with the combined phenotype of proliferative retinopathy and end-stage renal disease in U.K.-R.O.I. (odds ratio [OR] 1.14, P = 0.19) or FinnDiane (OR 1.06, P = 0.60). However, a fixed-effects meta-analysis that included the previously reported cohorts retained a genome-wide significant association with that phenotype (OR 1.31, P = 2 x 10(-9)). An expanded investigation of the ELMO1 locus and genetic regions reported to be associated with DN in the U.S. GoKinD yielded only nominal statistical significance for these loci. Finally, top candidates identified in a recent meta-analysis failed to reach genome-wide significance. In conclusion, we were unable to replicate most of the previously reported genetic associations for DN, and significance for the EPO promoter association was attenuated. Diabetes 61:2187-2194, 2012
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