Mo1122 INTEGRATED NETWORK ANALYSIS USING PATIENT-SPECIFIC SINGLE NUCLEOTIDE POLYMORPHISM PROFILES UNCOVERS NEW PATHWAYS INVOLVED IN ULCERATIVE COLITIS PATHOGENESIS

carcinoma", "lymphoma").NMSC was defined as "C44 other malignant neoplasms of skin".Heatmaps were created using R.The Crohn's disease risk allele was used as the reference allele.Significant associations, controlling for confounders of interest and population stratification, were then validated using individual level data in the UK Biobank.Results: Phenome wide association study (PheWas) followed by hierarchical clustering demonstrated a cluster of SNPs, which correlated with melanoma and other skin cancers.The highest risk was observed with rs2476601 ( PTPN22[W620R]) followed by rs35667974 ( IFIH1[I923V]), rs2188962, rs61839660 (IL2RA), rs34536443 (TYK2[P1104A]), and rs3812565.Expansion of the PheWas to include more specificity in each neoplasm category demonstrated that the cluster of SNPs initially associated with "melanoma and other skin cancers" was specific for NMSC.(Figure 1) Validation of SNPs was then performed using individual level data in the UK Biobank.There were 11,109 cases of NMSC and 398,525 controls.(Table 1) Significant clinical associations were seen between NMSC and age (OR 1.09, 95% CI 1.09,1.09),male gender (OR 1.26, 95% CI 1.21,1.31),and thiopurine use (OR 3.20, 95% CI 2.51,4.08).Using multivariate modeling, significant genetic associations were seen between rs35667974 (OR 1.14, 95% CI 1.04,1.24),rs2476601 (OR 1.09, 95% CI 1.04,1.14),rs61839660 (OR 1.06, 95% CI 1.01,1.10),rs3812565 (OR 1.05, 95% CI 1.02,1.08),and rs2188962 (OR 1.03, 95% CI 1,1.06) and NMSC independent from age, gender, and thiopurine use.Interaction terms between genotypes and thiopurine use were non-significant indicating that the effect of thiopurine medication on NMSC risk is likely to be independent of genotype.Discussion: Genetic variants in IFIH1, PTPN22, and IL2RA, which increase the risk of IBD and are associated with innate and adaptive immune responses, also confer increased risk for NMSC independent of thiopurine use.Further efforts to understand the shared pathogenesis between IBD and NMSC are needed.