A digestive condition most often caused by Helicobacter pylori infection or NSAID use — a 2021 UK Biobank GWAS of 456,327 people found genome-wide significant loci and, unusually, found the disease shares genetics with depression as well as with other digestive conditions.
Peptic ulcer disease (PUD) is a break in the lining of the stomach or upper small intestine. The two dominant, well-established causes are Helicobacter pylori infection and long-term NSAID use (nonsteroidal anti-inflammatory drugs) — genetics is a smaller contributor layered on top of those.
Wu et al. 2021 ran a genome-wide association study of peptic ulcer disease in 16,666 European-ancestry cases and 439,661 European-ancestry controls from the UK Biobank (456,327 people total). The three variants on this page were each genome-wide significant in that study: rs10500661 (near CNGA4, p=4×10⁻¹⁴), rs34074411 (near GAST, p=3×10⁻¹⁰) and rs9581957 (near URAD, p=4×10⁻⁹). At all three positions, GWAS Catalog's recorded allele was protective — associated with roughly 7–10% lower odds of peptic ulcer disease (odds ratios 0.90–0.93) rather than higher odds.
GAST encodes gastrin, the hormone that drives stomach acid secretion — a direct, plausible mechanistic link to an ulcer-forming disease. The paper's own title names its most striking finding, though: peptic ulcer disease shares genetic architecture not just with other digestive conditions but with depression, and separately with genetic susceptibility to H. pylori infection itself — an overlap this page reports as the paper's own headline claim rather than a number this page independently verified, since the full text sits behind a paywall this page could not open.
2026-01-27 · Genome-wide association and integrative analyses of relative handgrip strength identify polygenic determinants of gastrointestinal disorder susceptibility. BMC Gastroenterology. 2026. DOI:10.1186/s12876-026-04624-9
Hand grip strength (adjusted for BMI as relative hand grip strength, RHGS) is a marker of skeletal muscle quality, and this UK Biobank study of 405,394 Europeans set out to test whether it has a genuine causal relationship with digestive disorders, not just a correlation via general frailty. The GWAS itself found 1,111 independent SNPs across 226 loci and 407 genes; transcriptome-wide association prioritized L3MBTL3, CEP192 and NUCKS1, highly expressed in muscle cell types. The more clinically interesting results came from Mendelian randomization: genetically higher RHGS reduced the odds of diaphragmatic hernia (OR=0.45), diverticular intestine disease (OR=0.42), NAFLD (OR=0.49) and peptic ulcer (OR=0.54) -- a one-directional causal signal, not merely correlation. A polygenic risk score for RHGS replicated smaller but consistent protective associations with abdominal hernia, diaphragmatic hernia and diverticular disease. Notably, the protective effect was weakened by diabetes, high cholesterol and smoking, but strengthened by a cardioprotective diet and higher fiber intake -- muscle strength's protective effect on the gut is modifiable by lifestyle, not fixed. This site's hand grip strength page carries 59 variants; none of L3MBTL3, CEP192 or NUCKS1 are currently among them, and this is also a genuine new connection to the diverticular disease and peptic ulcer disease pages this site already has.
Peptic ulcer disease is diagnosed by endoscopy and tested for with an H. pylori breath, stool or biopsy test — not by genotype. None of the 3 variants on this page are used by any guideline to diagnose peptic ulcer disease or to decide treatment in an individual.
Treatment follows the cause: antibiotic eradication of H. pylori when it is present, and stopping or reducing NSAID use when that is the driver, both usually alongside acid-suppressing medication. The genetics found here describes population-level susceptibility on top of those two dominant, non-genetic causes — it does not change how any individual case is actually managed.
What a 23andMe/AncestryDNA export or raw VCF can and can't tell you about Peptic Ulcer Disease comes down to these specific, well-studied positions — not a diagnosis.
The studies behind these variants recruited participants from different ancestries — a result found in one population doesn't always transfer to another. Based on 3 of 3 linked studies with a resolved discovery ancestry.
Databases, guidelines and references
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Peptic Ulcer Disease. MyGeneLog™. https://www.mygenelog.com/conditions/peptic-ulcer-disease
Peptic ulcer disease is a break in the lining of the stomach or upper small intestine, most often caused by Helicobacter pylori infection or long-term NSAID use.
In 16,666 cases and 439,661 controls (456,327 people total), it found several genome-wide significant loci, including the three on this page, and reported that peptic ulcer disease shares genetic architecture with depression and with H. pylori infection susceptibility itself.
They lower it. GWAS Catalog's record for all three shows the named allele associated with roughly 7–10% lower odds (odds ratios 0.90 to 0.93), not higher odds.
No. Diagnosis is by endoscopy and H. pylori testing, and treatment follows the cause (antibiotics for infection, stopping NSAIDs when that's the driver) — not genotype.
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