ArticleHuman molecular genetics2012
Long-range DNA looping and gene expression analyses identify DEXI as an autoimmune disease candidate gene.
Article in Human molecular genetics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers, 3 of them syntheses that pooled it.
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Who cites it
70 citing papers in PubMed, 3 syntheses or guidelines pooled it, 110 citations in OpenAlex.
- Multiancestry association study identifies new asthma risk loci that colocalize with immune-cell enhancer marks.Nature genetics · 2018Pooled it
- Common variants at PVT1, ATG13-AMBRA1, AHI1 and CLEC16A are associated with selective IgA deficiency.Nature genetics · 2016Pooled it
- A method for gene-based pathway analysis using genomewide association study summary statistics reveals nine new type 1 diabetes associations.Genetic epidemiology · 2014Pooled it
- Analysis of chromatin structure reveals the connection between sQTLs and the splicing of distant genes.Scientific reports · 2025Article
- Functional dissection of noncoding variants associated with rheumatoid arthritis.Annals of the rheumatic diseases · 2025Article
- Is DEXI a Multiple Sclerosis Susceptibility Gene?International journal of molecular sciences · 2025Review
- Untangling the genetics of beta cell dysfunction and death in type 1 diabetes.Molecular metabolism · 2024Review
- Computational methods for identifying enhancer-promoter interactions.Quantitative biology (Beijing, China) · 2023Review
- Review
- 3D genome organization and epigenetic regulation in autoimmune diseases.Frontiers in immunology · 2023Review
- Chromosome conformation capture approaches to investigate 3D genome architecture in Ankylosing Spondylitis.Frontiers in genetics · 2023Article
- Genetic overlap between type 1 diabetes and other autoimmune diseases.Seminars in immunopathology · 2022Review
- A catalog of GWAS fine-mapping efforts in autoimmune disease.American journal of human genetics · 2021Review
- Immune Regulation in Time and Space: The Role of Local- and Long-Range Genomic Interactions in Regulating Immune Responses.Frontiers in immunology · 2021Review
- Chromatin Conformation in Development and Disease.Frontiers in cell and developmental biology · 2021Review
- Three-Dimensional Genome Interactions Identify Potential Adipocyte Metabolism-Associated GeneFrontiers in endocrinology · 2021Article
- Next steps in the identification of gene targets for type 1 diabetes.Diabetologia · 2020Review
- Discovery of non-HLA antibodies associated with cardiac allograft rejection and development and validation of a non-HLA antigen multiplex panel: From bench to bedside.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2020Article
- Clarifying the function of genes at the chromosome 16p13 locus in type 1 diabetes: CLEC16A and DEXI.Genes and immunity · 2020Article
- The type 1 diabetes candidate gene Dexi does not affect disease risk in the nonobese diabetic mouse model.Genes and immunity · 2020Article
10 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
69 authors at 8 institutions in 3 countries.
Funding
Abstract
The chromosome 16p13 region has been associated with several autoimmune diseases, including type 1 diabetes (T1D) and multiple sclerosis (MS). CLEC16A has been reported as the most likely candidate gene in the region, since it contains the most disease-associated single-nucleotide polymorphisms (SNPs), as well as an imunoreceptor tyrosine-based activation motif. However, here we report that intron 19 of CLEC16A, containing the most autoimmune disease-associated SNPs, appears to behave as a regulatory sequence, affecting the expression of a neighbouring gene, DEXI. The CLEC16A alleles that are protective from T1D and MS are associated with increased expression of DEXI, and no other genes in the region, in two independent monocyte gene expression data sets. Critically, using chromosome conformation capture (3C), we identified physical proximity between the DEXI promoter region and intron 19 of CLEC16A, separated by a loop of >150 kb. In reciprocal experiments, a 20 kb fragment of intron 19 of CLEC16A, containing SNPs associated with T1D and MS, as well as with DEXI expression, interacted with the promotor region of DEXI but not with candidate DNA fragments containing other potential causal genes in the region, including CLEC16A. Intron 19 of CLEC16A is highly enriched for transcription-factor-binding events and markers associated with enhancer activity. Taken together, these data indicate that although the causal variants in the 16p13 region lie within CLEC16A, DEXI is an unappreciated autoimmune disease candidate gene, and illustrate the power of the 3C approach in progressing from genome-wide association studies results to candidate causal genes.
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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.