SORBS1 gene, a new candidate for diabetic nephropathy: results from a
multi-stage genome-wide association study in patients with type 1 diabetes.
Authors Germain M, Pezzolesi MG, Sandholm N, McKnight AJ, Susztak K, Lajer M, Forsblom
C, Marre M, Parving HH, Rossing P, Toppila I, Skupien J, Roussel R, Ko YA, Ledo
N, Folkersen L, Civelek M, Maxwell AP, Tregouet DA, Groop PH, Tarnow L, Hadjadj
Submitted By Katalin Susztak on 12/10/2014
Status Published
Journal Diabetologia
Year 2015
Date Published 3/1/2015
Volume : Pages 58 : 543 - 8
PubMed Reference 25476525
Abstract The genetic determinants of diabetic nephropathy remain poorly understood. We
aimed to identify novel susceptibility genes for diabetic nephropathy., 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., 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?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?nephropathy. The minor rs1326934-C allele was less frequent in cases than in
controls (0.34 vs 0.43) and was associated with a decreased risk for diabetic
nephropathy (OR 0.70; 95% CI 0.60, 0.82). However, this association was not
observed in a second stage with two additional diabetic nephropathy cohorts, the
All Ireland-Warren 3-Genetics of Kidneys in Diabetes UK and Republic of Ireland
(UK-ROI; p?=?0.15) and the Finnish Diabetic Nephropathy (FinnDiane; p?=?0.44)
studies, totalling 2,142 cases and 2,494 controls. Altogether, the random-effect
meta-analysed rs1326934-C allele OR for diabetic nephropathy was 0.83 (95% CI
0.72, 0.96; p?=?0.009)., These data suggest that SORBS1 might be a gene involved
in diabetic nephropathy.

Investigators with authorship
Marcus PezzolesiUniversity of Utah
Katalin SusztakUniversity of Pennsylvania