Bidirectional association and shared risk factors between atrial fibrillation and heart failure: a Mendelian Randomization study

Background Atrial fibrillation and heart failure are closely related and share multiple risk factors. We aimed to apply the mendelian randomization (MR) analysis to explore the bidirectional causal link between atrial fibrillation and heart failure, and the independent effect of potential risk factors on the risk of both conditions. Methods This is a two-sample MR study using publicly available summary-level statistics of genome-wide association studies (GWAS). Bidirectional MR was performed to explore the relation between atrial fibrillation and heart failure. A total of 14 factors were selected as potential risk factors, univariable MR analyses were used to identify shared risk factors, and then the multivariable MR analyses were further used to investigate the independent effect of these factors on both conditions. Inverse-variance-weighted MR (IVW-MR) were used to obtain the effect estimates. Results MR analysis found evidence of causal relationship between atrial fibrillation and heart failure (odds ratio [OR], 1.24; 95% confidence interval [CI], 1.19–1.29), as well as between heart failure and atrial fibrillation (OR, 3.88; 95% CI, 1.45–10.37). Univariable MR analyses identified several shared risk factors for both conditions, including body mass index (BMI), blood pressure, smoking, coronary heart disease and myocardial infarction. After adjusting for atrial fibrillation, the observed associations between shared factors and heart failure kept stable, such as BMI, smoking, coronary heart disease and myocardial infarction. However, after adjusting for heart failure, the relationships between most risk factors and atrial fibrillation attenuated to null. Conclusions This two-sample MR study found a bidirectional relationship between atrial fibrillation and heart failure, and identified several shared risk factors of both conditions, which had an independent effect on the risk of heart failure while probably affected the risk of atrial fibrillation via cardiac impairment. Funding Start-up Fund for high-level talents of Fujian Medical University (grant no.XRCZX2021026) and Natural Science Foundation of Fujian Province (grant no. 2022J01706). ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This work was supported by the Natural Science Foundation of Fujian Province (grant no. 2022J01706) and the Start-up Fund for high-level talents of Fujian Medical University (XRCZX2021026) to Dr. Wuqing Huang. The funder had no role in study design, data collection and interpretation, or the decision to submit the work for publication. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: All these studies had been approved by the relevant institutional review boards and informed consent had been obtained for all participants per the original study protocols. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All raw summary-level data are available in the referenced public datasets, the detailed information of which could be found in [Supplementary File-Table 1][1]. The codes and curated data for the current analysis are available at . * BMI : body mass index CI : confidence interval GWAS : Genome-Wide Association Studies HbA1C : Glycosylated hemoglobin type A1C IVW-MR : inverse-variance weighted mendelian randomization MR : Mendelian randomization MR-PRESSO : MR-pleiotropy residual sum and outlier OR : odds ratio PM2.5 : Particulate matter 2.5 SNPs : single nucleotide polymorphisms. [1]: #T1