Common variants at the MHC locus and at chromosome 16q24.1 predispose to Barrett's esophagus
Copyright policy )Common variants at the MHC locus and at chromosome 16q24.1 predispose to Barrett's esophagus
Barrett's esophagus is an increasingly common disease that is strongly associated with reflux of stomach acid and usually a hiatus hernia, and it strongly predisposes to esophageal adenocarcinoma (EAC), a tumor with a very poor prognosis. We report the first genome-wide association study on Barrett's esophagus, comprising 1,852 UK cases and 5,172 UK controls in the discovery stage and 5,986 cases and 12,825 controls in the replication stage. Variants at two loci were associated with disease risk: chromosome 6p21, rs9257809 (Pcombined=4.09×10(-9); odds ratio (OR)=1.21, 95% confidence interval (CI)=1.13-1.28), within the major histocompatibility complex locus, and chromosome 16q24, rs9936833 (Pcombined=2.74×10(-10); OR=1.14, 95% CI=1.10-1.19), for which the closest protein-coding gene is FOXF1, which is implicated in esophageal development and structure. We found evidence that many common variants of small effect contribute to genetic susceptibility to Barrett's esophagus and that SNP alleles predisposing to obesity also increase risk for Barrett's esophagus.
- University of Sheffield United Kingdom
- University of Helsinki Finland
- Royal Victoria Infirmary United Kingdom
- Queen Elizabeth Hospital Birmingham United Kingdom
- Victoria Hospital United Kingdom
Male, obesity, genetic association, genotype, GASTROESOPHAGEAL-REFLUX DISEASE, genetic risk, Linkage Disequilibrium, Major Histocompatibility Complex, Gene Frequency, Models, single nucleotide polymorphism, genetic variability, POPULATION, EMC MM-03-47-02-A, Genome-wide association, allele, article, Single Nucleotide, Middle Aged, CANCER, major histocompatibility complex, Risk-factors, female, priority journal, OBESITY, /dk/atira/pure/sustainabledevelopmentgoals/good_health_and_well_being, Female, FOXF1 gene, Human, Adult, /dk/atira/pure/subjectarea/asjc/1300/1311, gene locus, 572, SUSCEPTIBILITY LOCI, name=Genetics, organogenesis, 610, EMC MM-04-20-01, EMC MM-04-47-07, Polymorphism, Single Nucleotide, Chromosomes, Article, Barrett Esophagus, Genetic, male, 1311 Genetics, SDG 3 - Good Health and Well-being, Humans, controlled study, Genetic Predisposition to Disease, Polymorphism, GENOME-WIDE ASSOCIATION, gene, METAANALYSIS, Aged, Barrett esophagus, Models, Genetic, Pair 16, ADENOCARCINOMA, IGMD 2: Molecular gastro-enterology and hepatology NCMLS 5: Membrane transport and intracellular motility, IGMD 2: Molecular gastro-enterology and hepatology ONCOL 3: Translational research, major clinical study, name=SDG 3 - Good Health and Well-being, Genetic Loci, Case-Control Studies, chromosome 6p, RISK-FACTORS, METAPLASIA, Susceptibility loci, genetic predisposition, Gastroesophageal-reflux disease, Chromosomes, Human, Pair 16, genetic susceptibility, Genome-Wide Association Study
Male, obesity, genetic association, genotype, GASTROESOPHAGEAL-REFLUX DISEASE, genetic risk, Linkage Disequilibrium, Major Histocompatibility Complex, Gene Frequency, Models, single nucleotide polymorphism, genetic variability, POPULATION, EMC MM-03-47-02-A, Genome-wide association, allele, article, Single Nucleotide, Middle Aged, CANCER, major histocompatibility complex, Risk-factors, female, priority journal, OBESITY, /dk/atira/pure/sustainabledevelopmentgoals/good_health_and_well_being, Female, FOXF1 gene, Human, Adult, /dk/atira/pure/subjectarea/asjc/1300/1311, gene locus, 572, SUSCEPTIBILITY LOCI, name=Genetics, organogenesis, 610, EMC MM-04-20-01, EMC MM-04-47-07, Polymorphism, Single Nucleotide, Chromosomes, Article, Barrett Esophagus, Genetic, male, 1311 Genetics, SDG 3 - Good Health and Well-being, Humans, controlled study, Genetic Predisposition to Disease, Polymorphism, GENOME-WIDE ASSOCIATION, gene, METAANALYSIS, Aged, Barrett esophagus, Models, Genetic, Pair 16, ADENOCARCINOMA, IGMD 2: Molecular gastro-enterology and hepatology NCMLS 5: Membrane transport and intracellular motility, IGMD 2: Molecular gastro-enterology and hepatology ONCOL 3: Translational research, major clinical study, name=SDG 3 - Good Health and Well-being, Genetic Loci, Case-Control Studies, chromosome 6p, RISK-FACTORS, METAPLASIA, Susceptibility loci, genetic predisposition, Gastroesophageal-reflux disease, Chromosomes, Human, Pair 16, genetic susceptibility, Genome-Wide Association Study
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