Fatty acids and risk of dilated cardiomyopathy: A two-sample Mendelian randomization study

Jiexin Zhang; Qiang Luo; Jun Hou; Wenjing Xiao; Pan Long; Yonghe Hu; Xin Chen; Han Wang

doi:10.3389/fnut.2023.1068050

Fatty acids and risk of dilated cardiomyopathy: A two-sample Mendelian randomization study

Front Nutr. 2023 Feb 16:10:1068050. doi: 10.3389/fnut.2023.1068050. eCollection 2023.

Authors

Jiexin Zhang^{1

2}, Qiang Luo¹, Jun Hou¹, Wenjing Xiao², Pan Long², Yonghe Hu², Xin Chen¹, Han Wang³

Affiliations

¹ Department of Laboratory Medicine, Affiliated Hospital of Southwest Jiaotong University, The Third People's Hospital of Chengdu, Chengdu, Sichuan, China.
² Central Laboratory, The General Hospital of Western Theater Command, Chengdu, Sichuan, China.
³ Department of Cardiology, Affiliated Hospital of Southwest Jiaotong University, The Third People's Hospital of Chengdu, Chengdu, Sichuan, China.

Abstract

Background: Previous observational studies have shown intimate associations between fatty acids (FAs) and dilated cardiomyopathy (DCM). However, due to the confounding factors and reverse causal association found in observational epidemiological studies, the etiological explanation is not credible.

Objective: To exclude possible confounding factors and reverse causal associations found in observational epidemiological studies, we used the two-sample Mendelian randomization (MR) analysis to verify the causal relationship between FAs and DCM risk.

Method: All data of 54 FAs were downloaded from the genome-wide association studies (GWAS) catalog, and the summary statistics of DCM were extracted from the HF Molecular Epidemiology for Therapeutic Targets Consortium GWAS. Two-sample MR analysis was conducted to evaluate the causal effect of FAs on DCM risk through several analytical methods, including MR-Egger, inverse variance weighting (IVW), maximum likelihood, weighted median estimator (WME), and the MR pleiotropy residual sum and outlier test (MRPRESSO). Directionality tests using MR-Steiger to assess the possibility of reverse causation.

Results: Our analysis identified two FAs, oleic acid and fatty acid (18:1)-OH, that may have a significant causal effect on DCM. MR analyses indicated that oleic acid was suggestively associated with a heightened risk of DCM (OR = 1.291, 95%CI: 1.044-1.595, P = 0.018). As a probable metabolite of oleic acid, fatty acid (18:1)-OH has a suggestive association with a lower risk of DCM (OR = 0.402, 95%CI: 0.167-0.966, P = 0.041). The results of the directionality test suggested that there was no reverse causality between exposure and outcome (P < 0.001). In contrast, the other 52 available FAs were discovered to have no significant causal relationships with DCM (P > 0.05).

Conclusion: Our findings propose that oleic acid and fatty acid (18:1)-OH may have causal relationships with DCM, indicating that the risk of DCM from oleic acid may be decreased by encouraging the conversion of oleic acid to fatty acid (18:1)-OH.

Keywords: dilated cardiomyopathy; genome-wide association studies; hydroxy fatty acid; oleic acid; two-sample Mendelian randomization.

Grants and funding

This research was supported by the Key R&D projects of Sichuan Provincial Department of Science and Technology (Nos. 2019YFS0542 and 2020YFS0122), the Key projects of Sichuan Provincial Health Commission (No. 19ZDXM0016), Sichuan Administration of Traditional Chinese Medicine (2020CP0003), and the basic research cultivation support program of Southwest Jiaotong University, special project of medical and industrial integration cultivation (LKPY2020-L).