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 tidsskrift › Letter › Forskning › fagfællebedømt
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> 10(-4))>
CONCLUSIONS/INTERPRETATION: These data suggest that SORBS1 might be a gene involved in diabetic nephropathy.
|Status||Udgivet - mar. 2015|