ArticlePloS one2014
Multiple functional risk variants in a SMAD7 enhancer implicate a colorectal cancer risk haplotype.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 40 citations in OpenAlex.
- Tissue-specific I-Smad mechanisms revealed by structure-function analysis inLife science alliance · 2026Article
- Early and late RNA eQTL are driven by different genetic mechanisms.Nature communications · 2026Article
- An evolving understanding of multiple causal variants underlying genetic association signals.American journal of human genetics · 2025Review
- Article
- Identification and characterization of colorectal-cancer-associated SNPs on the SMAD7 locus.Journal of cancer research and clinical oncology · 2023Article
- Article
- PEACOCK: a machine learning approach to assess the validity of cell type-specific enhancer-gene regulatory relationships.NPJ systems biology and applications · 2023Article
- A risk variant for Barrett's esophagus and esophageal adenocarcinoma at chr8p23.1 affects enhancer activity and implicates multiple gene targets.Human molecular genetics · 2022Article
- Functional genomic analysis delineates regulatory mechanisms of GWAS-identified bipolar disorder risk variants.Genome medicine · 2022Article
- Prioritization and functional analysis of GWAS risk loci for Barrett's esophagus and esophageal adenocarcinoma.Human molecular genetics · 2022Article
- Identification of potential functional variants and genes at 18q21.1 associated with the carcinogenesis of colorectal cancer.PLoS genetics · 2022Article
- Molecular regulation after mucosal injury and regeneration in ulcerative colitis.Frontiers in molecular biosciences · 2022Review
- Genome-Wide Association and Transcriptome-Wide Association Studies Identify Novel Susceptibility Genes Contributing to Colorectal Cancer.Journal of immunology research · 2022Article
- Role of Enhancers in Development and Diseases.Epigenomes · 2021Review
- A Functional Variant on 9p21.3 Related to Glioma Risk Affects Enhancer Activity and Modulates Expression of CDKN2B-AS1.Human mutation · 2021Article
- Article
- Non-Lynch Familial and Early-Onset Colorectal Cancer Explained by Accumulation of Low-Risk Genetic Variants.Cancers · 2021Article
- SNPs associated with colorectal cancer at 15q13.3 affect risk enhancers that modulate GREM1 gene expression.Human mutation · 2021Article
- Association of Body Mass Index With Colorectal Cancer Risk by Genome-Wide Variants.Journal of the National Cancer Institute · 2021Article
- Meta-Analyses of Splicing and Expression Quantitative Trait Loci Identified Susceptibility Genes of Glioma.Frontiers in genetics · 2021Article
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Authors and funding
10 authors at 5 institutions in 2 countries.
Funding
Abstract
Genome-wide association studies (GWAS) of colorectal cancer (CRC) have led to the identification of a number of common variants associated with modest risk. Several risk variants map within the vicinity of TGFβ/BMP signaling pathway genes, including rs4939827 within an intron of SMAD7 at 18q21.1. A previous study implicated a novel SNP (novel 1 or rs58920878) as a functional variant within an enhancer element in SMAD7 intron 4. In this study, we show that four SNPs including novel 1 (rs6507874, rs6507875, rs8085824, and rs58920878) in linkage disequilibrium (LD) with the index SNP rs4939827 demonstrate allele-specific enhancer effects in a large, multi-component enhancer of SMAD7. All four SNPs demonstrate allele-specific protein binding to nuclear extracts of CRC cell lines. Furthermore, some of the risk-associated alleles correlate with increased expression of SMAD7 in normal colon tissues. Finally, we show that the enhancer is responsive to BMP4 stimulation. Taken together, we propose that the associated CRC risk at 18q21.1 is due to four functional variants that regulate SMAD7 expression and potentially perturb a BMP negative feedback loop in TGFβ/BMP signaling pathways.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.