title: No evidence for association of OAS1 with type 1 diabetes in unaffected siblings or type 1 diabetic cases.
abstract: Type 1 diabetes is a common autoimmune disorder that is strongly clustered in families. As the sharing of alleles of the HLA class II genes cannot explain all of this aggregation, alleles of multiple other loci are involved. Recently, it was reported that an A/G splice-site single nucleotide polymorphism (SNP; rs10774671) in the OAS1 gene, encoding 2'5'-oligoadenylate synthetase, was associated with a protective effect against type 1 diabetes in unaffected siblings, and yet affected siblings showed random transmission. Since this finding is difficult to explain biologically, we genotyped the OAS1 SNP in 1,552 type 1 diabetic families from the U.K., U.S., Romania, and Norway and in 4,287 type 1 diabetic cases and 4,735 control subjects from the U.K. We found no evidence of association in either unaffected (relative risk 1.00; P = 0.94) or affected (1.00; P = 0.96) siblings or in the case-control study (odds ratio 0.99; P = 0.83). These results suggest that additional evidence of association of a low penetrance effect in common disease should be sought when the primary result comes from unaffected siblings in the absence of any effect in cases.
authors.affiliation: Juvenile Diabetes Research Foundation/Wellcome Trust Diabetes and Inflammation Laboratory, Cambridge Institute for Medical Research, Wellcome Trust/MRC Building, Addenbrooke's Hospital, Hills Road, Cambridge CB2 2XY, U.K.
authors.forename: Deborah J
authors.initials: DJ
authors.lastname: Smyth
authors.forename: Jason D
authors.initials: JD
authors.lastname: Cooper
authors.forename: Christopher E
authors.initials: CE
authors.lastname: Lowe
authors.forename: Sarah
authors.initials: S
authors.lastname: Nutland
authors.forename: Neil M
authors.initials: NM
authors.lastname: Walker
authors.forename: David G
authors.initials: DG
authors.lastname: Clayton
authors.forename: John A
authors.initials: JA
authors.lastname: Todd
mesh_terms: D015088:2',5'-Oligoadenylate Synthetase / Q000235:genetics*; D017398:Alternative Splicing; D016022:Case-Control Studies; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D005060:Europe; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D009679:Nuclear Family; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D012044:Regression Analysis; D012306:Risk; D035781:Siblings; D044465:White People
chemical_list: C475085:OAS1 protein, human; D015088:2',5'-Oligoadenylate Synthetase