title: Confirmation of genetic associations at ELMO1 in the GoKinD collection supports its role as a susceptibility gene in diabetic nephropathy.
abstract: OBJECTIVE
  To examine the association between single nucleotide polymorphisms (SNPs) in the engulfment and cell motility 1 (ELMO1) gene, a locus previously shown to be associated with diabetic nephropathy in two ethnically distinct type 2 diabetic populations, and the risk of nephropathy in type 1 diabetes.
  
  
  METHODS
  Genotypic data from a genome-wide association scan (GWAS) of the Genetics of Kidneys in Diabetes (GoKinD) study collection were analyzed for associations across the ELMO1 locus. In total, genetic associations were assessed using 118 SNPs and 1,705 individuals of European ancestry with type 1 diabetes (885 normoalbuminuric control subjects and 820 advanced diabetic nephropathy case subjects).
  
  
  RESULTS
  The strongest associations in ELMO1 occurred at rs11769038 (odds ratio [OR] 1.24; P = 1.7 x 10(-3)) and rs1882080 (OR 1.23; P = 3.2 x 10(-3)) located in intron 16. Two additional SNPs, located in introns 18 and 20, respectively, were also associated with diabetic nephropathy. No evidence of association for variants previously reported in type 2 diabetes was observed in our collection.
  
  
  CONCLUSIONS
  Using GWAS data from the GoKinD collection, we comprehensively examined evidence of association across the ELMO1 locus. Our investigation marks the third report of associations in ELMO1 with diabetic nephropathy, further establishing its role in the susceptibility of this disease. There is evidence of allelic heterogeneity, contributed by the diverse genetic backgrounds of the different ethnic groups examined. Further investigation of SNPs at this locus is necessary to fully understand the commonality of these associations and the mechanism(s) underlying their role in diabetic nephropathy.
authors: Research Division, Joslin Diabetes Center, and Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA.
authors: Marcus G
authors: MG
authors: Pezzolesi
authors: Pisut
authors: P
authors: Katavetin
authors: Masahiko
authors: M
authors: Kure
authors: G David
authors: GD
authors: Poznik
authors: Jan
authors: J
authors: Skupien
authors: Josyf C
authors: JC
authors: Mychaleckyj
authors: Stephen S
authors: SS
authors: Rich
authors: James H
authors: JH
authors: Warram
authors: Andrzej S
authors: AS
authors: Krolewski
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D001794:Blood Pressure; D002465:Cell Movement; D002648:Child; D002675:Child, Preschool; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics* / Q000503:physiopathology; D003928:Diabetic Nephropathies / Q000235:genetics*; D005006:Ethnicity / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study / Q000379:methods*; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007668:Kidney / Q000502:physiology / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012016:Reference Values; D044465:White People / Q000235:genetics
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D006442:Glycated Hemoglobin; C465214:ELMO1 protein, human