Final Report Summary - TRANS_CEDAR (Identifying Inflammatory Bowel Disease causative genes through trans-eQTLs mapping within GWAS loci)
Our eQTL dataset has also been used in assigning functional effects to causal variants detected in a fine mapping project for Crohn's disease and Ulcerative Colitis. We have found a slight enrichment in ciseQTLs effects in CD14, Illeum and rectum for SNPs detected by fine mapping. In particular, fine mapping variants that had significant eQTL effects were characterized in order to identify t the physiopahtological mechanism. This was addressed by looking for functional signatures in silico using publicly available datasets from Epigenome analysis initiatives (Wahsu epigenome browser, Blueprint and ). If the detected variants had epigenomic signatures in blood cell types or intestinal tissues, allellic imbanlance in available Chip seq data was analyzed with VGA tool. We have found an exmple which a fine mapping variant was located in a transcription binding site and this having a functional impact since there was an allelic imbalance in chip seq data in a lymphobalstoid cell line (62%; p=0,001, 100000 permutations)
Since samples come from healthy individuals, our dataset is equally useful for the study of other diseases and phenotypes. So far, CEDAR eQTL dataset utility has been expanded into three projects where the researcher has implemented similar statistical methods to identify SNPs responsible for eQTL effects in different scenarios. In particular, we tested the regulatory function of genome wide association variants for immune mediated disorders summarised in immunobase: We fitted GWAS variants as a covariate in ciseQTLs detected in the association region. In addition to that, we tested cis eQTLs enrichment in enhnacer regions detected through Hi-C. Finnally, cis eQTL analysis was used in order to evaluate the detected variants in the first genome wide study for renal rejection transplantation.