ArticlePloS one2016
Identification of Non-HLA Genes Associated with Celiac Disease and Country-Specific Differences in a Large, International Pediatric Cohort.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 68 citations in OpenAlex.
- Celiac Disease: A Comprehensive Review of Epidemiology, Pathogenesis, and Therapeutic Strategies.Digestive diseases and sciences · 2026Review
- Article
- Glucose Metabolic Enzyme PFKFB3 in Cardiopulmonary Vascular Health and Disease.Circulation research · 2026Review
- An integrated nutritional and performance monitoring framework for athletes with celiac disease: A structured narrative review.Current research in food science · 2026Review
- Innate immune dysregulation in celiac disease and refractory celiac disease: mechanisms, management and emerging therapies.Frontiers in immunology · 2026Review
- Rethinking Celiac Disease Management: Treatment Approaches Beyond the Gluten-Free Diet.Biomedicines · 2025Review
- Microbial associations and viruses on the risk of celiac disease (MAVRiC): a longitudinal post-hoc case-cohort study.Scientific reports · 2025Article
- Unfolding the Mystery of Autoimmunity: The Environmental Determinants of Diabetes in the Young (TEDDY) Study.Diabetes care · 2025Review
- Pancreatic Comorbidities in Pediatric Celiac Disease: Exocrine Pancreatic Insufficiency, Pancreatitis, and Diabetes Mellitus.Diagnostics (Basel, Switzerland) · 2025Review
- Altered miRNA expression in duodenal tissue of celiac patients and the impact of a gluten-free diet: a preliminary study.Molecular biology reports · 2025Article
- Looking back at the TEDDY study: lessons and future directions.Nature reviews. Endocrinology · 2025Review
- Risk of celiac disease autoimmunity is modified by interactions between CD247 and environmental exposures.Scientific reports · 2024Article
- Association ofGenes · 2024Article
- How the Microbiota May Affect Celiac Disease and What We Can Do.Nutrients · 2024Review
- From an understanding of etiopathogenesis to novel therapies-what is new in the treatment of celiac disease?Frontiers in pharmacology · 2024Review
- Coeliac disease: what can we learn from prospective studies about disease risk?The Lancet. Child & adolescent health · 2024Review
- Review article: Becoming and being coeliac-special considerations for childhood, adolescence and beyond.Alimentary pharmacology & therapeutics · 2022Review
- Genetically modified rodent models and celiac, non-celiac gluten sensitivity: a minireview.Central European journal of public health · 2022Review
- Integrated single-cell transcriptomics and epigenomics reveals strong germinal center-associated etiology of autoimmune risk loci.Science immunology · 2021Article
- Dissecting the contribution of single nucleotide polymorphisms inJournal of translational autoimmunity · 2021Article
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Authors and funding
19 authors at 10 institutions in 5 countries.
Funding
Abstract
objectivesThere are significant geographical differences in the prevalence and incidence of celiac disease that cannot be explained by HLA alone. More than 40 loci outside of the HLA region have been associated with celiac disease. We investigated the roles of these non-HLA genes in the development of tissue transglutaminase autoantibodies (tTGA) and celiac disease in a large international prospective cohort study.
methodsA total of 424,788 newborns from the US and European general populations and first-degree relatives with type 1 diabetes were screened for specific HLA genotypes. Of these, 21,589 carried 1 of the 9 HLA genotypes associated with increased risk for type 1 diabetes and celiac disease; we followed 8676 of the children in a 15 y prospective follow-up study. Genotype analyses were performed on 6010 children using the Illumina ImmunoChip. Levels of tTGA were measured in serum samples using radio-ligand binding assays; diagnoses of celiac disease were made based on persistent detection of tTGA and biopsy analysis. Data were analyzed using Cox proportional hazards analyses.
resultsWe found 54 single-nucleotide polymorphisms (SNPs) in 5 genes associated with celiac disease (TAGAP, IL18R1, RGS21, PLEK, and CCR9) in time to celiac disease analyses (10-4>P>5.8x10-6). The hazard ratios (HR) for the SNPs with the smallest P values in each region were 1.59, 1.45, 2.23, 2.64, and 1.40, respectively. Outside of regions previously associated with celiac disease, we identified 10 SNPs in 8 regions that could also be associated with the disease (P<10-4). A SNP near PKIA (rs117128341, P = 6.5x10-8, HR = 2.8) and a SNP near PFKFB3 (rs117139146, P<2.8x10-7, HR = 4.9) reached the genome-wide association threshold in subjects from Sweden. Analyses of time to detection of tTGA identified 29 SNPs in 2 regions previously associated with celiac disease (CTLA4, P = 1.3x10-6, HR = 0.76 and LPP, P = 2.8x10-5, HR = .80) and 6 SNPs in 5 regions not previously associated with celiac disease (P<10-4); non-HLA genes are therefore involved in development of tTGA.
conclusionsIn conclusion, using a genetic analysis of a large international cohort of children, we associated celiac disease development with 5 non-HLA regions previously associated with the disease and 8 regions not previously associated with celiac disease. We identified 5 regions associated with development of tTGA. Two loci associated with celiac disease progression reached a genome-wide association threshold in subjects from Sweden.
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