SORBS1 gene, a new candidate for diabetic nephropathy: results from a multi-stage genome-wide association study in patients with type 1 diabetes
Research output: Contribution to journal › Letter › Research › peer-review
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.
Original language | English |
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Journal | Diabetologia |
Volume | 58 |
Issue number | 3 |
Pages (from-to) | 543-8 |
Number of pages | 6 |
ISSN | 0012-186X |
DOIs | |
Publication status | Published - Mar 2015 |
- Diabetes Mellitus, Type 1, Diabetic Nephropathies, European Continental Ancestry Group, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Male, Microfilament Proteins, Middle Aged, Polymorphism, Single Nucleotide
Research areas
ID: 160479006