Causality of Genetically Determined Monounsaturated Fatty Acids on Risk of Cardiovascular Disease: A Mendelian Randomization Study

Background/Aim The possible association between serum monounsaturated fatty acids (MUFAs) and the risk of cardiovascular diseases (CVDs) has been examined in observational studies, which indicate controversial findings. In the current study, we used the Mendelian randomization (MR) analysis to determine the causal relationship of genetically determined serum MUFAs with the risk of various CVD outcomes, including angina, atherosclerotic, ischemic heart disease (IHD), myocardial infarction (MI), and high blood pressure (BP). Method The summary statistics dataset on the genetic variants related to serum MUFAs was used from the published GWAS of European descent in UK Biobank participants (N=114,999). Genetic variants underlying angina, atherosclerotic, IHD, MI, and BP events were ascertained using a GWAS dataset of 461,880 (case= 14,828, control= 447,052), 463,010 (case= 12,171, control= 450,839), 361,194 (case= 20,857, control= 340,337), 462,933 (case= 10,616, control= 452,317), and 461,880 (case= 124,227, control= 337,653) European descent participants from the UK Biobank, respectively. Results Our results showed that MUFAs were associated with angina [ORIVW= 1.005, 95% CI: 1.003– 1.007, p = <0.001; Cochran’s Q=23.89, p=0.717, I2=0.0%; Egger intercept= -0.0003, p=0.289], atherosclerotic [ORIVW= 1.005, 95% CI: 1.003–1.007, p = <0.001; Cochran’s Q=42.71, p=0.078, I2=27.4%; Egger intercept= -0.0004, p=0.146], IHD [ORIVW= 1.004, 95% CI: 1.001–1.007, p = 0.005; Cochran’s Q=42.75, p=0.172, I2=18.1%; Egger intercept= -0.0001, p=0.827], MI [ORIVW= 1.001, 95% CI: 0.999– 1.003, p = 0.199; Cochran’s Q= 23.03, p=0.631, I2=0.0%; Egger intercept= -0.0003, p=0.196], and BP [ORWM= 1.008, 95% CI: 1.001–1.015, p = 0.022; Cochran’s Q= 52.87, p=0.015, I2= 37.6%; Egger intercept= 0.0002, p=0.779]. These results remained consistent using different Mendelian randomization methods and sensitivity analyses. Conclusion In the present MR analysis, serum MUFA levels were associated with the risk of angina, atherosclerotic, IHD, MI, and BP. These findings prompt significant questions about the function of MUFAs in the progression of CVD events. Further research is required to elucidate the connections between MUFAs and CVD to contribute to health policy decisions in reducing CVD risk. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement Not applicable. ### 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: The original data used are publicly available at . 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 The original data used are publicly available at . The original contributions presented in the study are included in the article/Supplementary Material; The process of MR analyses and the results are publicly available through the following HTML link: