AUTHOR=Huang Jian 

TITLE=Assessment of the causal association between celiac disease and cardiovascular diseases

JOURNAL=Frontiers in Cardiovascular Medicine

VOLUME=Volume 9 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/cardiovascular-medicine/articles/10.3389/fcvm.2022.1017209

DOI=10.3389/fcvm.2022.1017209

ISSN=2297-055X

ABSTRACT=Background: Epidemiological studies have reported inconsistent results of the association between celiac disease (CD) and cardiovascular diseases. Moreover, the causality remains largely unknown. Therefore, we aimed to investigate whether CD is causally associated cardiovascular diseases, including ischemic stroke, large artery stroke, cardioembolic stroke, small vessel stroke, coronary heart disease, myocardial infarction, angina, heart failure, atrial fibrillation, and venous thromboembolism using an mendelian randomization (MR) approach.
Methods: Summary-level data for CD were derived from a large-sample genome-wide association study (GWAS) including 12041 CD cases and 12228 controls of European ancestry. The corresponding data for ischemic stroke (34217 cases and 406111 controls), large artery stroke (4373 cases and 406111 controls), cardioembolic stroke (7193 cases and 406111 controls), small vessel stroke (5386 cases and 192662 controls), coronary heart disease (22233 cases and 64762 controls), myocardial infarction (11622 cases and 187840 controls), angina (18168 cases and 187840 controls), heart failure (47309 cases and 930014 controls), atrial fibrillation (60620 cases and 970216 controls), and venous thromboembolism (9176 cases and 209616 controls) were obtained from the IEU GWAS database. We calculated the causal effect using the inverse variance weighted method. Sensitivity analyses and leave-one-out analyses were performed to ensure the consistency and robustness of causal estimates.
Results: The MR inverse variance weighted estimates indicated no causal effect of genetically predicted CD on ischemic stroke (OR=1.001, 95% CI: 0.984-1.018), large artery stroke (OR=1.003, 95% CI: 0.961-1.048), cardioembolic stroke (OR=1.009, 95% CI: 0.977-1.042), small vessel stroke (OR=1.023, 95% CI: 0.981-1.066), coronary heart disease (OR=0.995, 95% CI: 0.977-1.013), myocardial infarction (OR=0.994, 95% CI: 0.959-1.030), angina (OR=1.006, 95% CI: 0.981-1.032), heart failure (OR=0.999, 95% CI: 0.982-1.016), atrial fibrillation (OR=1.000, 95% CI: 0.990-1.011), and venous thromboembolism (OR=1.001, 95% CI: 0.971-1.032). Sensitivity analyses using the MR-Egger, weighted median, and simple mode methods yielded similar results. No evidence of horizontal pleiotropy was identified (MR Pleiotropy Residual Sum and Outlier global test and MR-Egger intercept with P>0.05). 
Conclusion: Our findings do not support a causal contribution of CD itself to ischemic stroke, large artery stroke, cardioembolic stroke, small vessel stroke, coronary heart disease, myocardial infarction, angina, heart failure, atrial fibrillation, and venous thromboembolism risk.