title: SORBS1 gene, a new candidate for diabetic nephropathy: results from a multi-stage genome-wide association study in patients with type 1 diabetes.
abstract: OBJECTIVE
  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
  These data suggest that SORBS1 might be a gene involved in diabetic nephropathy.
authors.affiliation: Sorbonne Université, UPMC Université Paris 06, UMR_S 1166, Team Genomics & Pathophysiology of Cardiovascular Diseases, Paris, France.
authors.forename: Marine
authors.initials: M
authors.lastname: Germain
authors.forename: Marcus G
authors.initials: MG
authors.lastname: Pezzolesi
authors.forename: Niina
authors.initials: N
authors.lastname: Sandholm
authors.forename: Amy J
authors.initials: AJ
authors.lastname: McKnight
authors.forename: Katalin
authors.initials: K
authors.lastname: Susztak
authors.forename: Maria
authors.initials: M
authors.lastname: Lajer
authors.forename: Carol
authors.initials: C
authors.lastname: Forsblom
authors.forename: Michel
authors.initials: M
authors.lastname: Marre
authors.forename: Hans-Henrik
authors.initials: HH
authors.lastname: Parving
authors.forename: Peter
authors.initials: P
authors.lastname: Rossing
authors.forename: Iiro
authors.initials: I
authors.lastname: Toppila
authors.forename: Jan
authors.initials: J
authors.lastname: Skupien
authors.forename: Ronan
authors.initials: R
authors.lastname: Roussel
authors.forename: Yi-An
authors.initials: YA
authors.lastname: Ko
authors.forename: Nora
authors.initials: N
authors.lastname: Ledo
authors.forename: Lasse
authors.initials: L
authors.lastname: Folkersen
authors.forename: Mete
authors.initials: M
authors.lastname: Civelek
authors.forename: Alexander P
authors.initials: AP
authors.lastname: Maxwell
authors.forename: David-Alexandre
authors.initials: DA
authors.lastname: Tregouet
authors.forename: Per-Henrik
authors.initials: PH
authors.lastname: Groop
authors.forename: Lise
authors.initials: L
authors.lastname: Tarnow
authors.forename: Samy
authors.initials: S
authors.lastname: Hadjadj
mesh_terms: D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000235:genetics*; D003928:Diabetic Nephropathies / Q000209:etiology / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D055106:Genome-Wide Association Study / Q000379:methods*; D006801:Humans; D008297:Male; D008840:Microfilament Proteins / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D044465:White People
chemical_list: D008840:Microfilament Proteins; C432967:SORBS1 protein, human