Chunk #20 — Results — Integrating Genetic and Network Data across Species to Inform GWA Discoveries — Identifying candidate susceptibility genes for T1D.
The absence of an association between a T1D-associated SNP and the HLC expression values corresponding to a candidate susceptibility gene for that SNP cannot be taken as strong evidence against the gene's candidacy as a susceptibility gene. The underlying causal change in DNA may not affect expression levels of the gene in question, or the variation in expression may be specific to a given tissue not profiled or to conditions not reflected in the HLC. However, strong associations between T1D-associated SNPs and expression levels of genes near the SNP provide direct functional support for a gene's involvement in disease susceptibility. For example, rs3764021 was identified as a T1D susceptibility locus in the WTCCC study and then extensively replicated [15]. CLEC2D was inferred as the most likely susceptibility gene at this locus. However, CLEC2D expression in the HLC data was not associated with this SNP; but a flanking gene, CLECL1 was significantly associated (p = 5.78 × 10−17; Table 1). Given that CLEC2D and CLECL1 are in the same gene family, the strong association between the T1D SNP and CLECL1 expression data suggest that CLECL1 may be a better candidate susceptibility gene to examine.
