ArticlePLoS genetics2014
Identification of a regulatory variant that binds FOXA1 and FOXA2 at the CDC123/CAMK1D type 2 diabetes GWAS locus.
Article in PLoS genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers, 4 of them syntheses that pooled it.
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Who cites it
58 citing papers in PubMed, 4 syntheses or guidelines pooled it, 100 citations in OpenAlex.
- Adipose tissue eQTL meta-analysis highlights the contribution of allelic heterogeneity to gene expression regulation and cardiometabolic traits.Nature genetics · 2025Pooled it
- The landscape of GWAS validation; systematic review identifying 309 validated non-coding variants across 130 human diseases.BMC medical genomics · 2022Pooled it
- Pooled it
- Genome-wide association analyses identify 143 risk variants and putative regulatory mechanisms for type 2 diabetes.Nature communications · 2018Pooled it
- CAMKK1 in Obesity and Type 2 Diabetes Mellitus: Evidence of Interaction With Appetite-Regulating, Metabolic and Inflammatory Factors.Endocrinology, diabetes & metabolism · 2025Article
- Genetic effects on chromatin accessibility uncover mechanisms of liver gene regulation and quantitative traits.Genome research · 2025Article
- Podocyte-specific KLF6 primes proximal tubule CaMK1D signaling to attenuate diabetic kidney disease.Nature communications · 2024Article
- Single cell multiome profiling of pancreatic islets reveals physiological changes in cell type-specific regulation associated with diabetes risk.bioRxiv : the preprint server for biology · 2024Article
- Characterizing genetic variation in the regulation of the ER stress response through computational and cis-eQTL analyses.G3 (Bethesda, Md.) · 2023Article
- Adipose tissue eQTL meta-analysis reveals the contribution of allelic heterogeneity to gene expression regulation and cardiometabolic traits.bioRxiv : the preprint server for biology · 2023Article
- Genome-wide association study and functional characterization identifies candidate genes for insulin-stimulated glucose uptake.Nature genetics · 2023Article
- The Type 2 Diabetes Knowledge Portal: An open access genetic resource dedicated to type 2 diabetes and related traits.Cell metabolism · 2023Article
- Loci for insulin processing and secretion provide insight into type 2 diabetes risk.American journal of human genetics · 2023Article
- Type 1 diabetes risk genes mediate pancreatic beta cell survival in response to proinflammatory cytokines.Cell genomics · 2022Article
- Combining SNP-to-gene linking strategies to identify disease genes and assess disease omnigenicity.Nature genetics · 2022Article
- Stem Cell-Derived β Cells: A Versatile Research Platform to Interrogate the Genetic Basis of β Cell Dysfunction.International journal of molecular sciences · 2022Review
- Integrated Bioinformatics Analysis Identifies Robust Biomarkers and Its Correlation With Immune Microenvironment in Nonalcoholic Fatty Liver Disease.Frontiers in genetics · 2022Article
- Functional characterization of T2D-associated SNP effects on baseline and ER stress-responsive β cell transcriptional activation.Nature communications · 2021Article
- Genetic effects on liver chromatin accessibility identify disease regulatory variants.American journal of human genetics · 2021Article
- Genetic Variants in Transcription Factor Binding Sites in Humans: Triggered by Natural Selection and Triggers of Diseases.International journal of molecular sciences · 2021Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
Many of the type 2 diabetes loci identified through genome-wide association studies localize to non-protein-coding intronic and intergenic regions and likely contain variants that regulate gene transcription. The CDC123/CAMK1D type 2 diabetes association signal on chromosome 10 spans an intergenic region between CDC123 and CAMK1D and also overlaps the CDC123 3'UTR. To gain insight into the molecular mechanisms underlying the association signal, we used open chromatin, histone modifications and transcription factor ChIP-seq data sets from type 2 diabetes-relevant cell types to identify SNPs overlapping predicted regulatory regions. Two regions containing type 2 diabetes-associated variants were tested for enhancer activity using luciferase reporter assays. One SNP, rs11257655, displayed allelic differences in transcriptional enhancer activity in 832/13 and MIN6 insulinoma cells as well as in human HepG2 hepatocellular carcinoma cells. The rs11257655 risk allele T showed greater transcriptional activity than the non-risk allele C in all cell types tested. Using electromobility shift and supershift assays we demonstrated that the rs11257655 risk allele showed allele-specific binding to FOXA1 and FOXA2. We validated FOXA1 and FOXA2 enrichment at the rs11257655 risk allele using allele-specific ChIP in human islets. These results suggest that rs11257655 affects transcriptional activity through altered binding of a protein complex that includes FOXA1 and FOXA2, providing a potential molecular mechanism at this GWAS locus.
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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.