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Genetic factors are recognized to contribute to peptic ulcer disease (PUD) and other gastrointestinal diseases, such as gastro-oesophageal reflux disease (GORD), irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD). Here, genome-wide association study (GWAS) analyses based on 456,327 UK Biobank (UKB) individuals identify 8 independent and significant loci for PUD at, or near, genes MUC1, MUC6, FUT2, PSCA, ABO, CDX2, GAST and CCKBR. There are previously established roles in susceptibility to Helicobacter pylori infection, response to counteract infection-related damage, gastric acid secretion or gastrointestinal motility for these genes. Only two associations have been previously reported for duodenal ulcer, here replicated trans-ancestrally. The results highlight the role of host genetic susceptibility to infection. Post-GWAS analyses for PUD, GORD, IBS and IBD add insights into relationships between these gastrointestinal diseases and their relationships with depression, a commonly comorbid disorder.

Original publication




Journal article


Nat Commun

Publication Date





ABO Blood-Group System, Antigens, Neoplasm, CDX2 Transcription Factor, Depression, Duodenal Ulcer, Female, Fucosyltransferases, GPI-Linked Proteins, Galactosyltransferases, Gastroesophageal Reflux, Gastrointestinal Diseases, Genetic Predisposition to Disease, Genome-Wide Association Study, Helicobacter Infections, Helicobacter pylori, Humans, Inflammatory Bowel Diseases, Male, Mucin-1, Mucin-6, Neoplasm Proteins, Peptic Ulcer