Chunk #21 — Results — Integrating Genetic and Network Data across Species to Inform GWA Discoveries — Identifying candidate susceptibility genes for T1D.
In cases where disease-associated traits and expression traits are scored in the same cohort, there is the potential to directly infer causal relationships between genes and disease [25]. However, even without disease trait data in tissue-specific cohorts like the HLC, an integrative genomics approach can be used to identify the most likely candidate susceptibility gene for a given locus. For example, one of the more novel regions associated with T1D from the WTCCC study was Chromosomes 12q13 (rs2292239). ERBB3, a receptor tyrosine-protein kinase with a presumed role in immune signaling, was identified as the most plausible susceptibility gene at this locus. While ERRB3 expression in the HLC was not associated with this SNP, the expression of a flanking gene, RPS26, was significantly associated with this SNP (p = 4.03 × 10−22; Table 1). In fact, 40% of the in vivo expression variation for RPS26 in the HLC was explained by this single T1D associated SNP, and this SNP was the most strongly associated with RPS26 expression out of the greater than 800,000 SNPs genotyped in the HLC, .
