Abstract
Background
Symptoms related with Gastro-esophageal reflux disease (GERD) were previously shown to be linked with increased risk for the 2019 coronavirus disease (COVID-19). We aim to interrogate the possibility of a shared genetic basis between GERD and COVID-19 outcomes.
Methods
Using published GWAS data for GERD (78 707 cases; 288 734 controls) and COVID-19 susceptibility (up to 32 494 cases; 1.5 million controls), we examined the genetic relationship between GERD and three COVID-19 outcomes: risk of developing severe COVID-19, COVID-19 hospitalization and overall COVID-19 risk. We estimated the genetic correlation between GERD and COVID-19 outcomes followed by Mendelian randomization (MR) analyses to assess genetic causality. Conditional analyses were conducted to examine whether known COVID-19 risk factors (obesity, smoking, type-II diabetes, coronary artery disease) can explain the relationship between GERD and COVID-19.
Results
We found small to moderate genetic correlations between GERD and COVID-19 outcomes (rg between 0.06–0.24). MR analyses revealed a OR of 1.15 (95% CI: 0.96–1.39) for severe COVID-19; 1.16 (1.01–1.34) for risk of COVID-19 hospitalization; 1.05 (0.97–1.13) for overall risk of COVID-19 per doubling of odds in developing GERD. The genetic correlation/associations between GERD and COVID-19 showed mild attenuation towards the null when obesity and smoking was adjusted for.
Conclusions
Susceptibility for GERD and risk of COVID-19 hospitalization were genetically correlated, with MR findings supporting a potential causal role between the two. The genetic association between GERD and COVID-19 was partially attenuated when obesity is accounted for, consistent with obesity being a major risk factor for both diseases.
Contributor Information
Jue-Sheng Ong, Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, 300 Herston Road, Herston, QLD 4006, Brisbane, Australia.
Puya Gharahkhani, Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, 300 Herston Road, Herston, QLD 4006, Brisbane, Australia.
Thomas L Vaughan, Department of Epidemiology, School of Public Health, University of Washington, Seattle, WA, USA.
David Whiteman, Department of Population Health, QIMR Berghofer Medical Research Institute, 300 Herston Road, Herston, QLD 4006, Brisbane, Australia.
Bradley J Kendall, Department of Medicine, The University of Queensland, , Herston, QLD 4006, Brisbane, Australia; Department of Gastroenterology and Hepatology, Princess Alexandra Hospital, Woolloongabba, QLD 4102, Brisbane, Australia.
Stuart MacGregor, Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, 300 Herston Road, Herston, QLD 4006, Brisbane, Australia.
Supplementary Material
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.