Abstract
Genome-wide association (GWA) studies provide insight into multigenic diseases through the identification of susceptibility genes and etiological pathways. In addition, identification of shared variants among autoimmune disorders provides insight into common disease pathways. We previously reported association of a nonsynonymous single nucleotide polymorphism (nsSNP) rs763361/Gly307Ser in the immune response gene
CD226
on chromosome 18q22 with type 1 diabetes (T1D) susceptibility. Here, we report efforts towards 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 (2,088 cases and 3,289 controls) and autoimmune thyroid disease (AITD) (821 cases and 1,920 controls), resulting in strong support for the Ser
307
association with T1D (
P
= 3.46 × 10
−9
) and continued potential evidence for AITD (
P
= 0.0345), we provide convincing evidence for association of Gly307Ser with MS (
P
= 4.20 × 10
−4
) and some evidence for another autoimmune disease, rheumatoid arthritis (RA) (
P
= 0.017). The Ser
307
allele of rs763361 in exon 7 of
CD226
predisposes to T1D, MS, possibly AITD and possibly RA, and based on the tag SNP analysis, could be the causal variant.
