Genome-wide association study of gastric cancer- and duodenal ulcer-derived<i>Helicobacter pylori</i>strains reveals discriminatory amino acid differences and novel oncoprotein candidates

<jats:title>Abstract</jats:title><jats:p>Genome-wide association studies (GWASs) can reveal genetic variations associated with a phenotype in the absence of any hypothesis of candidate genes. The problem of false-positive sites linked with the responsible site might be bypassed in bacteria with a high homologous recombination rate, such as<jats:italic>Helicobacter pylori</jats:italic>, which causes gastric cancer (GC). We conducted a GWAS followed by regression-based prediction of GC and duodenal ulcer<jats:italic>H. pylori</jats:italic>strains. We identified 14 single nucleotide polymorphisms (11 amino acid changes) that, combined, allowed effective disease discrimination. They were often informative of the underlying molecular mechanisms, such as electric charge alteration at the ligand-binding pocket, alteration in subunit interaction, and mode-switching of DNA methylation. We also identified three novel virulence factors/oncoprotein candidates. These results provide both defined targets for further informatic and experimental analyses to gain insights into GC pathogenesis and a basis for identifying a set of biomarkers for application in clinical settings.</jats:p>