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High Serum Monounsaturated Fatty Acids Levels May Increase Risk of Cardiovascular Disease: A Mendelian Randomization

Danial Habibi¹, Farshad Teymoori^2,3, Fahimeh Haghighatdoost⁴

¹Social Determinants of Health Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran.

Iranian Journal of Medical Sciences

|September 21, 2026

Abstract

Background:

Monounsaturated fatty acids (MUFAs) are dietary and circulating fats that may influence cardiovascular health. However, their causal role in cardiovascular diseases (CVDs) remains unclear due to conflicting observational evidence. This study aimed to determine the causal relationship of high serum MUFAs with the risk of various CVDs using the Mendelian randomization (MR) design.

Methods:

The summary statistics dataset related to serum MUFAs was used from the published genome-wide association study (GWAS) of European descent in UK Biobank participants (n=114,999). Genetic variants underlying angina, atherosclerotic, ischemic heart disease (IHD), myocardial infarction (MI), and hypertension 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. We investigated potential association relationships between MUFAs and these outcomes using generalized summary Mendelian randomization (GSMR) and two-sample Mendelian randomization (TSMR). TSMR was employed to validate associations identified by GSMR. The results were reported as odds ratios (ORs) with 95% confidence intervals (CIs).

Results:

GSMR results showed that MUFAs were associated with angina (OR=1.007, 95%CI:1.005-1.009; P<0.001), atherosclerotic (OR=1.006, 95%CI:1.004-1.008; P<0.001), IHD (OR=1.006, 95%CI:1.003-1.009; P<0.001), MI (OR=1.003, 95%CI:1.001-1.005; P<0.001), and hypertension (OR=1.003, 95%CI:0.998-1.008; P<0.001). Besides, TSMR results indicated that MUFAs were associated with angina (OR=1.012, 95%CI:1.010-1.015), atherosclerotic (OR=1.009, 95%CI:1.006-1.011; P<0.001), IHD (OR=1.015, 95%CI:1.010-1.019; P<0.001), MI (OR=1.007, 95%CI:1.004-1.009; P<0.001), and hypertension (OR=1.021, 95%CI:1.011-1.031; P<0.001). These findings remained consistent when utilizing different MR methods and sensitivity analyses.

Conclusion:

The current MR study indicated that higher levels of MUFAs might be associated with an increased risk of CVD events.Preprint Declaration: A preprint version of this manuscript is available at https://www.medrxiv.org/content/10.1101/2023.09.06.23295142v1.

Keywords:

Angina pectoris Cardiovascular diseases Hypertension Mendelian randomization analysis Monounsaturated fatty acids

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