Nishiyama Nina C, Silverstein Sophie, Darlington Kimberly, Kennedy Ng Meaghan M, Clough Katelyn M, Bauer Mikaela, Beasley Caroline, Bharadwaj Akshatha, Ganesan Rajee, Kapadia Muneera R, Lau Gwen, Lian Grace, Rahbar Reza, Sadiq Timothy S, Schaner Matthew R, Stem Jonathan, Friton Jessica, Faubion William A, Sheikh Shehzad Z, Furey Terrence S
Curriculum in Bioinformatics and Computational Biology, Department of Genetics, School of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Center for Gastrointestinal Biology and Disease, School of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
bioRxiv. 2024 Oct 17:2024.10.14.618229. doi: 10.1101/2024.10.14.618229.
Genome-wide association studies (GWAS) have identified over 300 loci associated with the inflammatory bowel diseases (IBD), but putative causal genes for most are unknown. We conducted the largest disease-focused expression quantitative trait loci (eQTL) analysis using colon tissue from 252 IBD patients to determine genetic effects on gene expression and potential contribution to IBD. Combined with two non-IBD colon eQTL studies, we identified 194 potential target genes for 108 GWAS loci. eQTL in IBD tissue were enriched for IBD GWAS loci colocalizations, provided novel evidence for IBD-associated genes such as and , and identified additional target genes compared to non-IBD tissue eQTL. IBD-associated eQTL unique to diseased tissue had distinct regulatory and functional characteristics with increased effect sizes. Together, these highlight the importance of eQTL studies in diseased tissue for understanding functional consequences of genetic variants, and elucidating molecular mechanisms and regulation of key genes involved in IBD.
全基因组关联研究（GWAS）已经确定了300多个与炎症性肠病（IBD）相关的基因座，但大多数基因座的推定因果基因尚不清楚。我们使用来自252名IBD患者的结肠组织进行了最大规模的疾病聚焦表达定量性状基因座（eQTL）分析，以确定基因对基因表达的影响以及对IBD的潜在贡献。结合两项非IBD结肠eQTL研究，我们为108个GWAS基因座确定了194个潜在靶基因。IBD组织中的eQTL在IBD GWAS基因座共定位中富集，为诸如 和 等IBD相关基因提供了新证据，并与非IBD组织eQTL相比确定了其他靶基因。患病组织特有的IBD相关eQTL具有不同的调控和功能特征，效应大小增加。总之，这些突出了患病组织中eQTL研究对于理解遗传变异的功能后果以及阐明IBD相关关键基因的分子机制和调控的重要性。
