Association Testing of Previously Reported Variants in a Large Case-Control Meta-analysis of Diabetic Nephropathy

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Association Testing of Previously Reported Variants in a Large Case-Control Meta-analysis of Diabetic Nephropathy

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Title: Association Testing of Previously Reported Variants in a Large Case-Control Meta-analysis of Diabetic Nephropathy
Author: Williams, Winfred W.; 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; Florez, Jose C.

Note: Order does not necessarily reflect citation order of authors.

Citation: 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.
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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.
Published Version: doi:10.2337/db11-0751
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3402313/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:11855856
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