Nonalcoholic fatty liver disease and cardiovascular diseases: A Mendelian randomization study

• Published in: Metabolism, clinical and experimental Vol. 133; p. 155220
• Main Authors: Peng, Hexiang, Wang, Siyue, Wang, Mengying, Ye, Ying, Xue, Enci, Chen, Xi, Wang, Xueheng, Fan, Meng, Gao, Wenjing, Qin, Xueying, Wu, Yiqun, Chen, Dafang, Li, Jin, Hu, Yonghua, Wang, Li, Wu, Tao
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.08.2022
• Subjects: Arterial stiffness; Cardiovascular Diseases - epidemiology; Cardiovascular Diseases - genetics; Coronary Artery Disease; Coronary heart disease; Genome-Wide Association Study; Heart Failure; Humans; Ischemic Stroke; Mendelian randomization; Mendelian Randomization Analysis; NAFLD; Non-alcoholic Fatty Liver Disease - epidemiology; Non-alcoholic Fatty Liver Disease - genetics; Polymorphism, Single Nucleotide; Stroke; Heart failure; NAFLD; Stroke; Mendelian randomization; Arterial stiffness; Coronary heart disease
• ISSN: 0026-0495; 1532-8600
• DOI: 10.1016/j.metabol.2022.155220

Evidence suggests that nonalcoholic fatty liver disease (NAFLD) is associated with cardiovascular diseases (CVDs). However, the results are inconsistent, and the causality remains to be established. We aimed to investigate the potential causal relationship between NAFLD and CVDs, including arterial stiffness, coronary artery disease, heart failure, stroke, ischemic stroke and its subtypes using two-sample Mendelian randomization (MR). Genetic instruments were used as proxies for NAFLD. Publicly available summary-level data were obtained from the UK Biobank, the CARDIoGRAMplusC4D Consortium, the MEGASTROKE Consortium, and other consortia. Six complementary MR methods were performed, including inverse variance weighted method (IVW), MR-Egger, weighted median, weighted mode, MR-PRESSO, and MR-RAPS. NAFLD was significantly associated with arterial stiffness (β = 0.04 [95%CI, 0.02–0.06], P = 5.53E-04). Moreover, the results remained consistent and robust in the sensitivity analysis. As for heart failure, the IVW method suggested that NAFLD was significantly associated with heart failure (OR = 1.08, 95%CI: 1.02–1.14, P = 0.005) in the absence of pleiotropy. However, there were no significant associations of NAFLD with coronary artery disease, stroke, ischemic stroke, or any ischemic stroke subtype. The MR study supported the causal effect of NAFLD on arterial stiffness. However, the study did not provide enough evidence suggesting the causal associations of NAFLD with heart failure, coronary artery disease, and any stroke subtypes. •Mendelian randomization was performed for the causal effect of NAFLD on CVD events.•The study strongly supported the causal effect of NAFLD on arterial stiffness.•In the study, NAFLD was not causally associated with CAD, heart failure, stroke, and its subtypes.