ArticleBMJ open diabetes research & care2014
Two novel type 2 diabetes loci revealed through integration of TCF7L2 DNA occupancy and SNP association data.
Article in BMJ open diabetes research & care, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers, 1 of them a synthesis that pooled it.
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Who cites it
7 citing papers in PubMed, 1 synthesis or guideline pooled it, 19 citations in OpenAlex.
- A Powerful Procedure for Pathway-Based Meta-analysis Using Summary Statistics Identifies 43 Pathways Associated with Type II Diabetes in European Populations.PLoS genetics · 2016Pooled it
- Innovative approaches to metabolic dysfunction-associated steatohepatitis diagnosis and stratification.Non-coding RNA research · 2025Article
- LncRNA and mRNA expression profiles in brown adipose tissue of obesity-prone and obesity-resistant mice.iScience · 2022Article
- CPPED1-targeting microRNA-371a-5p expression in human placenta associates with spontaneous delivery.PloS one · 2020Article
- Association between the UBE2Z rs46522 and TCF7L2 rs7903146 polymorphisms with type 2 diabetes in south western Iran.African health sciences · 2019Article
- Rs46522 in the Ubiquitin-Conjugating Enzyme E2Z Gene Is Associated with the Risk of Coronary Artery Disease in Individuals of Chinese Han Population with Type 2 Diabetes.Journal of diabetes research · 2017Article
- Multi-label multi-instance transfer learning for simultaneous reconstruction and cross-talk modeling of multiple human signaling pathways.BMC bioinformatics · 2015Article
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundThe transcription factor 7-like 2 (TCF7L2) locus is strongly implicated in the pathogenesis of type 2 diabetes (T2D). We previously mapped the genomic regions bound by TCF7L2 using ChIP (chromatin immunoprecipitation)-seq in the colorectal carcinoma cell line, HCT116, revealing an unexpected highly significant over-representation of genome-wide association studies (GWAS) loci associated primarily with endocrine (in particular T2D) and cardiovascular traits.
methodsIn order to further explore if this observed phenomenon occurs in other cell lines, we carried out ChIP-seq in HepG2 cells and leveraged ENCODE data for five additional cell lines. Given that only a minority of the predicted genetic component to most complex traits has been identified to date, plus our GWAS-related observations with respect to TCF7L2 occupancy, we investigated if restricting association analyses to the genes yielded from this approach, in order to reduce the constraints of multiple testing, could reveal novel T2D loci.
resultsWe found strong evidence for the continued enrichment of endocrine and cardiovascular GWAS categories, with additional support for cancer. When investigating all the known GWAS loci bound by TCF7L2 in the shortest gene list, derived from HCT116, the coronary artery disease-associated variant, rs46522 at the UBE2Z-GIP-ATP5G1-SNF8 locus, yielded significant association with T2D within DIAGRAM. Furthermore, when we analyzed tag-SNPs (single nucleotide polymorphisms) in genes not previously implicated by GWAS but bound by TCF7L2 within 5 kb, we observed a significant association of rs4780476 within CPPED1 in DIAGRAM.
conclusionsChIP-seq data generated with this GWAS-implicated transcription factor provided a biologically plausible method to limit multiple testing in the assessment of genome-wide genotyping data to uncover two novel T2D-associated loci.
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