ArticleJournal of the National Cancer Institute2024
Novel insights into genetic susceptibility for colorectal cancer from transcriptome-wide association and functional investigation.
Article in Journal of the National Cancer Institute, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 12 citations in OpenAlex.
- Mixed-model and transcriptome-wide association analyses identify transcription factors and genes associated with colorectal cancer susceptibility.Nature communications · 2026Article
- Multi-ancestry genome-wide and transcriptome-wide association analyses identified new risk loci and genes for inflammatory bowel disease.medRxiv : the preprint server for health sciences · 2025Article
- Multi-tissue expression and splicing data prioritise anatomical subsite- and sex-specific colorectal cancer susceptibility genes.Nature communications · 2025Article
- Meteorin-β: A Novel Biomarker and Therapeutic Target on Its Way to the Regulation of Human Diseases.International journal of molecular sciences · 2025Review
- Deciphering the Oncogenic Landscape of Hepatocytes Through Integrated Single-Nucleus and Bulk RNA-Seq of Hepatocellular Carcinoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Enhancing disease risk gene discovery by integrating transcription factor-linked trans-variants into transcriptome-wide association analyses.Nucleic acids research · 2025Article
- Article
- Fine-mapping analysis including over 254,000 East Asian and European descendants identifies 136 putative colorectal cancer susceptibility genes.Nature communications · 2024Article
- [Construction of a fecal protein Luminex liquid chip detection system for early diagnosis of colorectal tumors].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2023Article
- Plasma Bacterial DNA Load as a Potential Biomarker for the Early Detection of Colorectal Cancer: A Case-Control Study.Microorganisms · 2023Article
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Authors and funding
29 authors at 15 institutions in 8 countries.
Funding
Abstract
backgroundTranscriptome-wide association studies have been successful in identifying candidate susceptibility genes for colorectal cancer (CRC). To strengthen susceptibility gene discovery, we conducted a large transcriptome-wide association study and an alternative splicing transcriptome-wide association study in CRC using improved genetic prediction models and performed in-depth functional investigations.
methodsWe analyzed RNA-sequencing data from normal colon tissues and genotype data from 423 European descendants to build genetic prediction models of gene expression and alternative splicing and evaluated model performance using independent RNA-sequencing data from normal colon tissues of the Genotype-Tissue Expression Project. We applied the verified models to genome-wide association studies (GWAS) summary statistics among 58 131 CRC cases and 67 347 controls of European ancestry to evaluate associations of genetically predicted gene expression and alternative splicing with CRC risk. We performed in vitro functional assays for 3 selected genes in multiple CRC cell lines.
resultsWe identified 57 putative CRC susceptibility genes, which included the 48 genes from transcriptome-wide association studies and 15 genes from splicing transcriptome-wide association studies, at a Bonferroni-corrected P value less than .05. Of these, 16 genes were not previously implicated in CRC susceptibility, including a gene PDE7B (6q23.3) at locus previously not reported by CRC GWAS. Gene knockdown experiments confirmed the oncogenic roles for 2 unreported genes, TRPS1 and METRNL, and a recently reported gene, C14orf166.
conclusionThis study discovered new putative susceptibility genes of CRC and provided novel insights into the biological mechanisms underlying CRC development.
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