SORBS1 gene, a new candidate for diabetic nephropathy: results from a multi-stage genome-wide association study in patients with type 1 diabetes

Publikation: Bidrag til tidsskriftLetterForskningfagfællebedømt

  • Marine Germain
  • Marcus G Pezzolesi
  • Niina Sandholm
  • Amy J McKnight
  • Katalin Susztak
  • Maria Lajer
  • Carol Forsblom
  • Michel Marre
  • Hans-Henrik Parving
  • Iiro Toppila
  • Jan Skupien
  • Ronan Roussel
  • Yi-An Ko
  • Nora Ledo
  • Lasse Folkersen
  • Mete Civelek
  • Alexander P Maxwell
  • David-Alexandre Tregouet
  • Per-Henrik Groop
  • Lise Tarnow
  • Samy Hadjadj

AIMS/HYPOTHESIS: The genetic determinants of diabetic nephropathy remain poorly understood. We aimed to identify novel susceptibility genes for diabetic nephropathy.

METHODS: We performed a genome-wide association study using 1000 Genomes-based imputation to compare type 1 diabetic nephropathy cases with proteinuria and with or without renal failure with control patients who have had diabetes for more than 15 years and no evidence of renal disease.

RESULTS: None of the single nucleotide polymorphisms (SNPs) tested in a discovery cohort composed of 683 cases and 779 controls reached genome-wide statistical significance. The 46 top hits (p < 10(-5)) were then sought for first-stage analysis in the Genetics of Kidneys in Diabetes US (US-GoKinD) study, an independent population of 820 cases and 885 controls. Two SNPs in strong linkage disequilibrium with each other and located in the SORBS1 gene were consistently and significantly (p < 10(-4)) (0.34 (95% (finndiane; (or (uk-roi; 0.43) 0.60, 0.70; 0.72, 0.82). 0.83 0.96; 2,142 2,494 3-genetics 95% a additional all allele altogether, and associated association cases ci cohorts, controls controls. decreased diabetes diabetic finnish for frequent however, in ireland ireland-warren kidneys less meta-analysed minor nephropathy nephropathy. not observed of or p =" 0.009).</p" random-effect republic risk rs1326934-c second stage studies, than the this totalling two uk vs was with>

CONCLUSIONS/INTERPRETATION: These data suggest that SORBS1 might be a gene involved in diabetic nephropathy.

OriginalsprogEngelsk
TidsskriftDiabetologia
Vol/bind58
Udgave nummer3
Sider (fra-til)543-8
Antal sider6
ISSN0012-186X
DOI
StatusUdgivet - mar. 2015

ID: 160479006