P136 EPSTEIN-BARR VIRUS TRANSCRIPTION CO-FACTORS BIND TO MANY INFLAMMATORY BOWEL DISEASE RISK LOCI

Abstract Objective IBD is a chronic inflammatory disorder of the GI tract with complex etiology that involves both genetic variants and environmental factors. Several viruses and bacteria have been suggested as potential causes of the disease. The clinical course of IBD appears to be influenced by EBV tissue infection. With a prevalence of >90% in the adult human population, EBV infection is nearly ubiquitous. We reported that the EBV transcription co-factor EBNA2 was concentrated in the risk loci of IBD relative to the remainder of the genome (Pc=1.24E-13, (RR) = 3.33, Nature Genetics 50:699, 2018). The objective of this study was to determine whether new data and studies made available since the data used for our 2018 study further supported the possibility that EBV was related to some IBD as a potential etiologic agent. Methods Genomic approaches offer previously unavailable perspectives for understanding disease mechanisms. The previous analysis was based upon the 9 viral transcription factor and co-factor (TF) datasets available in human cells in 2015.Of the 52 now available there are 29 from EBV. The number of established IBD loci qualifying for analysis has expanded from 112 in 2015 to 324 available now. We applied simulation analysis to assess statistical significance of TF associations with IBD risk loci using RELI (Regulatory Element Locus Intersection) (Nat Genet 50:699, 2018). RELI tests the probability of the observed association by the count of intersections of the same variant from two sources. We extracted 700 SNPs in European ancestry from 93 published GWAS and 350 additional candidate gene studies for IBD. All variants with linkage disequilibrium r2>0.8 of the best variant were included, while loci with r2>0.2 with a more highly significant locus were excluded. Results Among the 52 viral TF datasets, 139 of the 324 IBD loci were occupied by EBNALP (RR=2.08793, Pc=3.7321E-23), 113 by EBNA3C (RR=2.35113, Pc=2.84678E-22), 88 loci by EBNA2 (RR=3.2, Pc=7.8E-32) and 28 loci by EBNA3ABC, which used an antibody that did not distinguish between EBNA3 subtypes. Analysis of 11,535 human TF ChIP-seq datasets produced 1578 with strong associations (p