Newly identified genetic risk variants for celiac disease related to the immune response
Copyright policy )Newly identified genetic risk variants for celiac disease related to the immune response
Our genome-wide association study of celiac disease previously identified risk variants in the IL2-IL21 region. To identify additional risk variants, we genotyped 1,020 of the most strongly associated non-HLA markers in an additional 1,643 cases and 3,406 controls. Through joint analysis including the genome-wide association study data (767 cases, 1,422 controls), we identified seven previously unknown risk regions (P < 5 x 10(-7)). Six regions harbor genes controlling immune responses, including CCR3, IL12A, IL18RAP, RGS1, SH2B3 (nsSNP rs3184504) and TAGAP. Whole-blood IL18RAP mRNA expression correlated with IL18RAP genotype. Type 1 diabetes and celiac disease share HLA-DQ, IL2-IL21, CCR3 and SH2B3 risk regions. Thus, this extensive genome-wide association follow-up study has identified additional celiac disease risk variants in relevant biological pathways.
- University of Bristol United Kingdom
- Queen Mary University of London United Kingdom
- University of London United Kingdom
- Amsterdam UMC Netherlands
- Imperial College London United Kingdom
Male, PROTEIN, population, MOUSE, Polymerase Chain Reaction, Linkage Disequilibrium, ACTIVATION, Cohort Studies, Mice, b-lymphocytes, Immunology, Inflammation & Infection, POPULATION, region, Chromosome Mapping, Genes & Society, Female, International Development, EXPRESSION, Genetic Markers, replication, Immunology, 610, B-LYMPHOCYTES, Polymorphism, Single Nucleotide, Interleukin-12 Subunit p35, REGION, Inflammation & Infection, HLA-DQ Antigens, expression, Genetics, Animals, Humans, Genetic Predisposition to Disease, GENOME-WIDE ASSOCIATION, Interleukin-18 Receptor beta Subunit, mouse, Genome, Human, 500, RHEUMATOID-ARTHRITIS, Celiac Disease, Diabetes Mellitus, Type 1, Case-Control Studies, REPLICATION, genome-wide association, rheumatoid-arthritis, activation, protein, Biomarkers
Male, PROTEIN, population, MOUSE, Polymerase Chain Reaction, Linkage Disequilibrium, ACTIVATION, Cohort Studies, Mice, b-lymphocytes, Immunology, Inflammation & Infection, POPULATION, region, Chromosome Mapping, Genes & Society, Female, International Development, EXPRESSION, Genetic Markers, replication, Immunology, 610, B-LYMPHOCYTES, Polymorphism, Single Nucleotide, Interleukin-12 Subunit p35, REGION, Inflammation & Infection, HLA-DQ Antigens, expression, Genetics, Animals, Humans, Genetic Predisposition to Disease, GENOME-WIDE ASSOCIATION, Interleukin-18 Receptor beta Subunit, mouse, Genome, Human, 500, RHEUMATOID-ARTHRITIS, Celiac Disease, Diabetes Mellitus, Type 1, Case-Control Studies, REPLICATION, genome-wide association, rheumatoid-arthritis, activation, protein, Biomarkers
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