Work

Novel insight into the gene etiology of ulcerative colitis gained from transcriptome association study and single-cell sequence analysis

Year: 2025

Type: article

Abstract: Ulcerative colitis (UC) is a prevalent chronic gastrointestinal disease. Gene plays an important role in UC pathogenesis. Therefore, we aim to identify UC susceptibility genes and specific cell types expressing these genes. We conducted a cross-tissue transcriptome-wide association study by integrating UC GWAS with 49 tissues gene expression matrix from the Genotype-Tissue Expression project. Subsequently, we employed Functional Summary-based Imputation to verify candidate genes within colon tissue. Conditional and Joint Analysis was utilized to filter out genes potentially influenced by linkage disequilibrium. Multimarker Analysis of Genomic Annotation was then applied to pinpoint genes relevant to UC. Validation of the selected genes was performed using Mendelian randomization. GeneMANIA analysis was conducted to elucidate biological functions of identified genes. Finally, single-cell RNA sequencing was employed to ascertain cell types in which these genes are enriched. The cross-tissue transcriptome-wide association study, Functional Summary-based Imputation and Multimarker Analysis of Genomic Annotation analyses identified a total of 5 genes, of which 3 genes, ADCY3, ITGB6, and MTMR3, were retained after Mendelian randomization. These genes were found to be implicated in several functional pathways, including the cyclic AMP metabolic process and phosphorus-oxygen lyase activity. Furthermore, we observed ADCY3 predominantly enriched in B cells, while ITGB6 and MTMR3 enriched in epithelial cells. Our study has identified 3 genes associated with UC susceptibility. These findings not only enhance our understanding of the genetic underpinnings of UC, but also offer novel avenues for exploring molecular mechanisms and potential therapeutic targets for UC.

Source: Medicine

DOI: 10.1097/md.0000000000046678

Authors: Donghui Ren, Zhenhua Dong, Miao Wang, Cong Fu, Yuchao Xin

Institution: First Hospital of Jilin University

Language: English

Topic: Inflammatory Bowel Disease

Subfield: Genetics

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $1,950