Association testing of previously reported variants in a large case-control meta-analysis of diabetic nephropathy

Research output: Contribution to journalArticle

Researchers

  • Winfred W. Williams
  • Rany M. Salem
  • Amy Jayne McKnight
  • Niina Sandholm
  • Carol Forsblom
  • Andrew Taylor
  • Candace Guiducci
  • Jarred B. McAteer
  • Gareth J. McKay
  • Tamara Isakova
  • Eoin P. Brennan
  • Denise M. Sadlier
  • Cameron D. Palmer
  • Jenny Söderlund
  • Emma Fagerholm
  • Valma Harjutsalo
  • Raija Lithovius
  • Daniel Gordin
  • Kustaa Hietala
  • Janne Kytö
  • And 20 others
  • Maija Parkkonen
  • Milla Rosengård-Bärlund
  • Lena Thorn
  • Anna Syreeni
  • Nina Tolonen
  • Markku Saraheimo
  • Johan Wadén
  • Janne Pitkäniemi
  • Cinzia Sarti
  • Jaakko Tuomilehto
  • Karl Tryggvason
  • Anne May Österholm
  • Bing He
  • Steve Bain
  • Finian Martin
  • Catherine Godson
  • Joel N. Hirschhorn
  • Alexander P. Maxwell
  • Per-Henrik Groop
  • Jose C. Florez

Research units

  • Harvard University
  • Broad Institute
  • Queen's University Belfast
  • University of Helsinki
  • University of Miami
  • University College Dublin
  • National Institute for Health and Welfare
  • South Ostrobothnia Central Hospital
  • Karolinska Institutet
  • Swansea University
  • Biomedicum Helsinki

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 genomewide 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.

Details

Original languageEnglish
Pages (from-to)2187-2194
Number of pages8
JournalDIABETES
Volume61
Issue number8
Publication statusPublished - Aug 2012
MoE publication typeA1 Journal article-refereed

ID: 13536866