Association Testing of Previously Reported Variants in a Large Case-Control Meta-analysis of Diabetic Nephropathy
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Author
Salem, Rany M.
McKnight, Amy Jayne
Sandholm, Niina
Forsblom, Carol
Taylor, Andrew
Guiducci, Candace
McAteer, Jarred B.
McKay, Gareth J.
Isakova, Tamara
Brennan, Eoin P.
Sadlier, Denise M.
Palmer, Cameron
Söderlund, Jenny
Fagerholm, Emma
Harjutsalo, Valma
Lithovius, Raija
Gordin, Daniel
Hietala, Kustaa
Kytö, Janne
Parkkonen, Maija
Rosengård-Bärlund, Milla
Thorn, Lena
Syreeni, Anna
Tolonen, Nina
Saraheimo, Markku
Wadén, Johan
Pitkäniemi, Janne
Sarti, Cinzia
Tuomilehto, Jaakko
Tryggvason, Karl
Österholm, Anne-May
He, Bing
Bain, Steve
Martin, Finian
Godson, Catherine
Hirschhorn, Joel N.
Maxwell, Alexander P.
Groop, Per-Henrik
Note: Order does not necessarily reflect citation order of authors.
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https://doi.org/10.2337/db11-0751Metadata
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Williams, W. W., R. M. Salem, A. J. McKnight, N. Sandholm, C. Forsblom, A. Taylor, C. Guiducci, et al. 2012. “Association Testing of Previously Reported Variants in a Large Case-Control Meta-analysis of Diabetic Nephropathy.” Diabetes 61 (8): 2187-2194. doi:10.2337/db11-0751. http://dx.doi.org/10.2337/db11-0751.Abstract
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 × 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.Other Sources
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3402313/pdf/Terms of Use
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