ArticleGenes and immunity2019
Prioritizing Crohn's disease genes by integrating association signals with gene expression implicates monocyte subsets.
Article in Genes and immunity, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 19 citations in OpenAlex.
- Development and functional adaptation of intestinal macrophages across the lifespan.Clinical & translational immunology · 2026Review
- The relationship between extreme inter-individual variation in macrophage gene expression and genetic susceptibility to inflammatory bowel disease.Human genetics · 2024Article
- Transcriptome-wide association studies associated with Crohn's disease: challenges and perspectives.Cell & bioscience · 2024Review
- Macrophages in intestinal homeostasis and inflammatory bowel disease.Nature reviews. Gastroenterology & hepatology · 2023Review
- CLUH functions as a negative regulator of inflammation in human macrophages and determines ulcerative colitis pathogenesis.JCI insight · 2023Article
- Identifying high-impact variants and genes in exomes of Ashkenazi Jewish inflammatory bowel disease patients.Nature communications · 2023Article
- Adipokine C1q/Tumor Necrosis Factor- Related Protein 3 (CTRP3) Attenuates Intestinal Inflammation Via Sirtuin 1/NF-κB Signaling.Cellular and molecular gastroenterology and hepatology · 2023Article
- Interpretation of the role of germline and somatic non-coding mutations in cancer: expression and chromatin conformation informed analysis.Clinical epigenetics · 2022Review
- Article
- Whole-Genome DNA Methylation Profiling of CD14+ Monocytes Reveals Disease Status and Activity Differences in Crohn's Disease Patients.Journal of clinical medicine · 2020Article
- Reaching the End-Game for GWAS: Machine Learning Approaches for the Prioritization of Complex Disease Loci.Frontiers in genetics · 2020Review
- Zebrafish modeling of intestinal injury, bacterial exposures and medications defines epithelialDisease models & mechanisms · 2019Article
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Authors and funding
17 authors at 10 institutions in 2 countries.
Funding
Abstract
Genome-wide association studies have identified ~170 loci associated with Crohn's disease (CD) and defining which genes drive these association signals is a major challenge. The primary aim of this study was to define which CD locus genes are most likely to be disease related. We developed a gene prioritization regression model (GPRM) by integrating complementary mRNA expression datasets, including bulk RNA-Seq from the terminal ileum of 302 newly diagnosed, untreated CD patients and controls, and in stimulated monocytes. Transcriptome-wide association and co-expression network analyses were performed on the ileal RNA-Seq datasets, identifying 40 genome-wide significant genes. Co-expression network analysis identified a single gene module, which was substantially enriched for CD locus genes and most highly expressed in monocytes. By including expression-based and epigenetic information, we refined likely CD genes to 2.5 prioritized genes per locus from an average of 7.8 total genes. We validated our model structure using cross-validation and our prioritization results by protein-association network analyses, which demonstrated significantly higher CD gene interactions for prioritized compared with non-prioritized genes. Although individual datasets cannot convey all of the information relevant to a disease, combining data from multiple relevant expression-based datasets improves prediction of disease genes and helps to further understanding of disease pathogenesis.
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