title: CD226 Gly307Ser association with multiple autoimmune diseases.
abstract: Genome-wide association studies provide insight into multigenic diseases through the identification of susceptibility genes and etiological pathways. In addition, the identification of shared variants among autoimmune disorders provides insight into common disease pathways. We previously reported an association of a nonsynonymous single nucleotide polymorphism (SNP) rs763361/Gly307Ser in the immune response gene CD226 on chromosome 18q22 with type 1 diabetes (T1D) susceptibility. Here, we report efforts toward identifying the causal variant by exonic resequencing and tag SNP mapping of the 18q22 region in both T1D and multiple sclerosis (MS). In addition to the analysis of newly available samples in T1D (2088 cases and 3289 controls) and autoimmune thyroid disease (AITD) (821 cases and 1920 controls), resulting in strong support for the Ser(307) association with T1D (P=3.46 x 10(-9)) and continued potential evidence for AITD (P=0.0345), we provide evidence for association of Gly307Ser with MS (P=4.20 x 10(-4)) and rheumatoid arthritis (RA) (P=0.017). The Ser(307) allele of rs763361 in exon 7 of CD226 predisposes to T1D, MS, and possibly AITD and RA, and based on the tag SNP analysis, could be the causal variant.
authors.affiliation: Juvenile Diabetes Research Foundation/Wellcome Trust Diabetes and Inflammation Laboratory, Cambridge Institute for Medical Research, Addenbrooke's Hospital, University of Cambridge, Cambridge, UK. jason.hafler@cimr.cam.ac.uk
authors.forename: J P
authors.initials: JP
authors.lastname: Hafler
authors.forename: L M
authors.initials: LM
authors.lastname: Maier
authors.forename: J D
authors.initials: JD
authors.lastname: Cooper
authors.forename: V
authors.initials: V
authors.lastname: Plagnol
authors.forename: A
authors.initials: A
authors.lastname: Hinks
authors.forename: M J
authors.initials: MJ
authors.lastname: Simmonds
authors.forename: H E
authors.initials: HE
authors.lastname: Stevens
authors.forename: N M
authors.initials: NM
authors.lastname: Walker
authors.forename: B
authors.initials: B
authors.lastname: Healy
authors.forename: J M M
authors.initials: JM
authors.lastname: Howson
authors.forename: M
authors.initials: M
authors.lastname: Maisuria
authors.forename: S
authors.initials: S
authors.lastname: Duley
authors.forename: G
authors.initials: G
authors.lastname: Coleman
authors.forename: S C L
authors.initials: SC
authors.lastname: Gough
authors.forename: J
authors.initials: J
authors.lastname: Worthington
authors.forename: V K
authors.initials: VK
authors.lastname: Kuchroo
authors.forename: L S
authors.initials: LS
authors.lastname: Wicker
authors.forename: J A
authors.initials: JA
authors.lastname: Todd
mesh_terms: D000483:Alleles; D000945:Antigens, Differentiation, T-Lymphocyte / Q000235:genetics*; D001327:Autoimmune Diseases / Q000235:genetics* / Q000276:immunology; D016022:Case-Control Studies; D002887:Chromosomes, Human, Pair 18; D016001:Confidence Intervals; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000276:immunology; D005091:Exons; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D009103:Multiple Sclerosis / Q000235:genetics / Q000276:immunology; D016017:Odds Ratio; D020161:Physical Chromosome Mapping; D020641:Polymorphism, Single Nucleotide; D000098862:T Lineage-Specific Activation Antigen 1
chemical_list: D000945:Antigens, Differentiation, T-Lymphocyte; D000098862:T Lineage-Specific Activation Antigen 1