OP11 Expanded genome-wide association study of Inflammatory Bowel Disease identifies 174 novel loci and directly implicates new genes in disease susceptibility

Abstract

i011 compared. Multivariate logistic regression was used to model the relationship between individual biologics and one-year outcomes, adjusted for potential confounders of EH, including disease duration, concomi-tant corticosteroid use, and prior anti-TNF failure. Results: Compared to vedolizumab [10/77 (13%)], both infliximab [29/79 (36.7%), aOR: 3.27 (95% CI: 1.34-8.01), p<0.001] and adali-mumab [12/40 (30%), aOR: 3.01 (95% CI: 1.10-8.21), p=0.032] were superior for achieving one-year EH of the ileum among patients with ileal involvement at baseline. No difference was observed between ustekinumab [5/22 (22.7%)] and vedolizumab [aOR: 2.75 (95% CI: 0.76-9.91), p=0.123]. In biologic-naïve patients, ustekinumab, adali-mumab, and infliximab were superior to vedolizumab for achieving one-year EH of the ileum. For colonic disease, in comparison to usteki-numab [9/31 (29.0%), adalimumab [30/48 (62.5%), aOR: 4.04 (95% CI: 1.88-8.71), p<0.001] and infliximab (55/105 (52.4%), aOR: 2.02 (95% CI: 1.03-3.99), p=0.041] were superior for one-year EH in the colon among patients with colonic involvements at baseline. No difference was seen between vedolizumab [26/87 (29.9%)] and ustekinumab [aOR: 1.01 (95% CI: 0.39-2.59), p=0.987]. Similar differences were noted among biologic-naïve patients. Conclusion: In this post-hoc analysis of pivotal clinical trials, TNFα antagonists were generally superior to vedolizumab and ustekinumab for achieving EH of the ileum and colon in patients with CD. However, among biologic-naïve patients, ustekinumab, adalimumab, and infliximab were superior to vedolizumab for attaining one-year EH of the ileum. Background: Genome-wide association studies (GWASs) have identified 243 loci associated with inflammatory bowel disease (IBD). However, the mapping of additional disease loci and causal variants is still limited by sample size. Larger GWAS can provide further insights into causal biology. Methods: We performed a GWAS meta-analysis of 33 cohorts, totalling 54,439 IBD patients (N=30,574 with Crohn's disease (CD), 21,193 with Ulcerative Colitis (UC)) and 37,054 European controls. Genotype imputation was undertaken using the TOPMed diverse population panel and association tests were performed using REGENIE. These results were meta-analysed with summary statistics from 4 additional studies, a Danish cohort, the UK Biobank, deCODE, and FinnGen, totalling 73,030 IBD patients and 1 million controls, Fig1.