Multiple common variants for celiac disease influencing immune gene expression
Copyright policy )Multiple common variants for celiac disease influencing immune gene expression
We performed a second-generation genome-wide association study of 4,533 individuals with celiac disease (cases) and 10,750 control subjects. We genotyped 113 selected SNPs with P(GWAS) < 10(-4) and 18 SNPs from 14 known loci in a further 4,918 cases and 5,684 controls. Variants from 13 new regions reached genome-wide significance (P(combined) < 5 x 10(-8)); most contain genes with immune functions (BACH2, CCR4, CD80, CIITA-SOCS1-CLEC16A, ICOSLG and ZMIZ1), with ETS1, RUNX3, THEMIS and TNFRSF14 having key roles in thymic T-cell selection. There was evidence to suggest associations for a further 13 regions. In an expression quantitative trait meta-analysis of 1,469 whole blood samples, 20 of 38 (52.6%) tested loci had celiac risk variants correlated (P < 0.0028, FDR 5%) with cis gene expression.
- Amsterdam UMC Netherlands
- University of California, San Francisco United States
- University College Dublin Ireland
- University Federico II of Naples Italy
- Trinity College Dublin Ireland
Risk, POSITIVE SELECTION, SUSCEPTIBILITY LOCI, Immunology, HETERODIMER, celiac disease; gene, 610, Gene Expression, Genes, MHC Class I, Medical and Health Sciences, Polymorphism, Single Nucleotide, Article, Meta-Analysis as Topic; Gene Expression; Risk; Gene Expression Profiling; Genes, MHC Class I; Celiac Disease; Polymorphism, Single Nucleotide; Genome-Wide Association Study; Humans; Case-Control Studies, MHC Class I, Meta-Analysis as Topic, Inflammation & Infection, Immunology, Inflammation & Infection, Genetics, RISK VARIANTS, celiac risk variants, 2.1 Biological and endogenous factors, Humans, Aetiology, Polymorphism, GENOME-WIDE ASSOCIATION, gene, POPULATION, THYMUS, Gene Expression Profiling, Human Genome, Single Nucleotide, Biological Sciences, ALLELES, THYMOCYTES, RHEUMATOID-ARTHRITIS, Celiac Disease, Genes, Case-Control Studies, genome-wide association rheumatoid-arthritis susceptibility loci positive selection risk variants population alleles thymus heterodimer thymocytes, Genes & Society, International Development, Digestive Diseases, celiac disease, Biotechnology, Developmental Biology, Genome-Wide Association Study
Risk, POSITIVE SELECTION, SUSCEPTIBILITY LOCI, Immunology, HETERODIMER, celiac disease; gene, 610, Gene Expression, Genes, MHC Class I, Medical and Health Sciences, Polymorphism, Single Nucleotide, Article, Meta-Analysis as Topic; Gene Expression; Risk; Gene Expression Profiling; Genes, MHC Class I; Celiac Disease; Polymorphism, Single Nucleotide; Genome-Wide Association Study; Humans; Case-Control Studies, MHC Class I, Meta-Analysis as Topic, Inflammation & Infection, Immunology, Inflammation & Infection, Genetics, RISK VARIANTS, celiac risk variants, 2.1 Biological and endogenous factors, Humans, Aetiology, Polymorphism, GENOME-WIDE ASSOCIATION, gene, POPULATION, THYMUS, Gene Expression Profiling, Human Genome, Single Nucleotide, Biological Sciences, ALLELES, THYMOCYTES, RHEUMATOID-ARTHRITIS, Celiac Disease, Genes, Case-Control Studies, genome-wide association rheumatoid-arthritis susceptibility loci positive selection risk variants population alleles thymus heterodimer thymocytes, Genes & Society, International Development, Digestive Diseases, celiac disease, Biotechnology, Developmental Biology, Genome-Wide Association Study
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