TY - JOUR
T1 - SORBS1 gene, a new candidate for diabetic nephropathy
T2 - results from a multi-stage genome-wide association study in patients with type 1 diabetes
AU - Germain, Marine
AU - Pezzolesi, Marcus G.
AU - Sandholm, Niina
AU - McKnight, Amy J.
AU - Susztak, Katalin
AU - Lajer, Maria
AU - Forsblom, Carol
AU - Marre, Michel
AU - Parving, Hans Henrik
AU - Rossing, Peter
AU - Toppila, Iiro
AU - Skupien, Jan
AU - Roussel, Ronan
AU - Ko, Yi An
AU - Ledo, Nora
AU - Folkersen, Lasse
AU - Civelek, Mete
AU - Maxwell, Alexander P.
AU - Tregouet, David Alexandre
AU - Groop, Per Henrik
AU - Tarnow, Lise
AU - Hadjadj, Samy
PY - 2015/1/1
Y1 - 2015/1/1
N2 - 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) associated with diabetic 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).Conclusions/interpretation: These data suggest that SORBS1 might be a gene involved in diabetic nephropathy.
AB - 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) associated with diabetic 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).Conclusions/interpretation: These data suggest that SORBS1 might be a gene involved in diabetic nephropathy.
KW - Diabetic nephropathy
KW - GWAS
KW - Kidney
KW - Sorbin
KW - Type 1 diabetes
UR - http://www.scopus.com/inward/record.url?scp=84925519441&partnerID=8YFLogxK
U2 - 10.1007/s00125-014-3459-6
DO - 10.1007/s00125-014-3459-6
M3 - Article
C2 - 25476525
AN - SCOPUS:84925519441
VL - 58
SP - 543
EP - 548
JO - Diabetologia
JF - Diabetologia
SN - 0012-186X
IS - 3
ER -