Causal effect of non-alcoholic fatty liver disease on atrial fibrillation

Non-alcoholic fatty liver disease (NAFLD) includes a range of liver pathologies based on non-alcoholic fatty liver, defined by the presence of fat accumulation in more than 5% of hepatocytes by non-invasive imaging or histological assessment [ [1] Reeder S.B. Sirlin C.B. Quantification of liver fat with magnetic resonance imaging. Magn Reson Imaging Clin N Am. 2010; 18 (ix): 337-357https://doi.org/10.1016/j.mric.2010.08.013 Abstract Full Text Full Text PDF PubMed Scopus (221) Google Scholar ]. The global prevalence of NAFLD is approximately 25%, and NAFLD is the leading cause of cirrhosis and hepatocellular carcinoma [ [2] Powell E.E. Wong V.W. Rinella M. Non-alcoholic fatty liver disease. Lancet. 2021; 397: 2212-2224https://doi.org/10.1016/S0140-6736(20)32511-3 Abstract Full Text Full Text PDF PubMed Scopus (482) Google Scholar ]. NAFLD is considered the hepatic manifestation of the metabolic syndrome. However, the liver is not only a passive target but affects the pathogenesis of the metabolic syndrome and its complications [ [3] Dietrich P. Hellerbrand C. Non-alcoholic fatty liver disease, obesity and the metabolic syndrome. Best Pract Res Clin Gastroenterol. 2014; 28: 637-653https://doi.org/10.1016/j.bpg.2014.07.008 Crossref PubMed Scopus (291) Google Scholar ]. Previous studies showed that there were mechanistic links between metabolic syndrome and atrial fibrillation (AF) susceptibility [ [4] Hajhosseiny R. Matthews G.K. Lip G.Y. Metabolic syndrome, atrial fibrillation, and stroke: tackling an emerging epidemic. Heart Rhythm. 2015; 12: 2332-2343https://doi.org/10.1016/j.hrthm.2015.06.038 Abstract Full Text Full Text PDF PubMed Scopus (28) Google Scholar ]. NAFLD as the hepatic manifestation of metabolic syndrome, has been regarded as the essential element of liver-heart axis [ [5] Ismaiel A. Dumitraşcu D.L. Cardiovascular risk in fatty liver disease: the liver-heart axis-literature review. Front Med (Lausanne). 2019; 6: 202https://doi.org/10.3389/fmed.2019.00202 Crossref PubMed Scopus (79) Google Scholar ]. AF is the most common cardiac arrhythmia. There were growing evidences of observational studies suggested that NAFLD was strongly associated with increased risk for AF [ [6] Käräjämäki A.J. Hukkanen J. Ukkola O. The association of non-alcoholic fatty liver disease and atrial fibrillation: a review. Ann Med. 2018; 50: 371-380https://doi.org/10.1080/07853890.2018.1492147 Crossref PubMed Scopus (16) Google Scholar , [7] Choi J. Lee S.R. Choi E.K. Ahn H.J. Kwon S. Park S.H. Lee H. Chung J. Han M. Lee S.W. Han K.D. Oh S. Lip G.Y.H. Non-alcoholic fatty liver disease and the risk of incident atrial fibrillation in young adults: a nationwide population-based cohort study. Front Cardiovasc Med. 2022; 9832023https://doi.org/10.3389/fcvm.2022.832023 Crossref Scopus (3) Google Scholar ]. However, it is difficult to evaluate the causality of NAFLD on AF due to the potential confounding biases that exist in observational studies. Mendelian Randomization (MR) analysis is a good tool to evaluate causality of risk factors on disease by using genetic variants as instrumental variables for risk factors. Because the genetic variants are assigned randomly at conception, MR analysis can reduce potential unmeasured confounders, a major limitation of evidence from observational studies. In this study, we aimed to evaluate the causal effect of NAFLD on AF using MR analysis.