Bourgeois, Stephane, Carr, Daniel F, Musumba, Crispin O, Penrose, Alexander, Esume, Celestine, Morris, Andrew P, Jorgensen, Andrea L ORCID: 0000-0002-6977-9337, Zhang, J Eunice ORCID: 0000-0003-1813-2207, Pritchard, D Mark ORCID: 0000-0001-7971-3561, Deloukas, Panos et al (show 1 more authors)
(2021)
Genome-Wide association between EYA1 and Aspirin-induced peptic ulceration.
EBioMedicine, 74.
p. 103728.
Text
FINAL PUBLISHED VERSION.pdf - Published version Download (1MB) | Preview |
Abstract
<h4>Background</h4>Low-dose aspirin can cause gastric and duodenal ulceration, hereafter called peptic ulcer disease (PUD). Predisposition is thought to be related to clinical and genetic factors; our aim was to identify genetic risk factors associated with aspirin-induced PUD.<h4>Methods</h4>Patients (n=1478) were recruited from 15 UK hospitals. Cases (n=505) were defined as patients with endoscopically confirmed PUD within 2 weeks of using aspirin and non-aspirin Non-Steroidal Anti-Inflammatory Drugs (NSAIDs). They were compared to two control groups: patients with endoscopically confirmed PUD without any history of NSAID use within 3 months of diagnosis (n=495), and patients with no PUD on endoscopy (n=478). A genome-wide association study (GWAS) of aspirin-induced cases (n=247) was compared to 476 controls. The results were validated by replication in another 84 cases and 162 controls.<h4>Findings</h4>The GWAS identified one variant, rs12678747 (p=1·65×10<sup>-7</sup>) located in the last intron of EYA1 on chromosome 8. The association was replicated in another sample of 84 PUD patients receiving aspirin (p=0·002). Meta-analysis of discovery and replication cohort data for rs12678747, yielded a genome-wide significant association (p=3·12×10<sup>-11</sup>; OR=2·03; 95% CI 1·65-2·50). Expression of EYA1 was lower at the gastric ulcer edge when compared with the antrum.<h4>Interpretation</h4>Genetic variation in an intron of the EYA1 gene increases the risk of endoscopically confirmed aspirin-induced PUD. Reduced EYA1 expression in the upper gastrointestinal epithelium may modulate risk, but the functional basis of this association will need mechanistic evaluation.<h4>Funding</h4>Department of Health Chair in Pharmacogenetics, MRC Centre for Drug Safety Science and the Barts Cardiovascular NIHR Biomedical Research Centre, British Heart Foundation (BHF).
Item Type: | Article |
---|---|
Uncontrolled Keywords: | NSAID, ulcer, Aspirin, GWAS |
Divisions: | Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Population Health Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology |
Depositing User: | Symplectic Admin |
Date Deposited: | 16 Dec 2021 10:57 |
Last Modified: | 18 Jan 2023 21:19 |
DOI: | 10.1016/j.ebiom.2021.103728 |
Related URLs: | |
URI: | https://livrepository.liverpool.ac.uk/id/eprint/3145478 |