The association between fatty acids and atherosclerotic diseases: A mendelian randomization study

• Published in: Clinical nutrition ESPEN 2024-10, Vol.63, p.447-456
• Main Authors: Wang, Yinyu, Yang, Bo, Wang, Cuiping
• Format: Article
• Language: English
• Subjects: Atherosclerosis - genetics; Atherosclerotic disease; clinical nutrition; coronary disease; docosahexaenoic acid; Fatty acid; Fatty Acids; Genetic analysis; Genome-Wide Association Study; Humans; Mendelian randomization; Mendelian Randomization Analysis; monounsaturated fatty acids; pleiotropy; Polymorphism, Single Nucleotide; Risk Factors; stroke; Stroke - epidemiology; Stroke - genetics; therapeutics
• ISSN: 2405-4577; 2405-4577
• DOI: 10.1016/j.clnesp.2024.06.018

The current observational studies have disputed the relationship between various fatty acids and atherosclerotic diseases, and the causal relationship between the two is still unclear. In this study, we utilized the available genome-wide association studies (GWAS) summary data on fatty acids and atherosclerotic diseases from the IEU OpenGWAS project. After identifying the appropriate single nucleotide polymorphisms (SNPs) as instrumental variables, we employed the MR-PRESSO outlier test to remove extreme values. Subsequently, we conducted a two-sample mendelian randomization (MR) analysis and performed sensitivity analyses to ensure the reliability of the results. The results of MR analysis suggest that ratio of saturated fatty acids to total fatty acids is positively correlated with the incidence rate of coronary heart disease (OR = 1.341, 95% CI = 1.016–1.769, P value = 0.038), monounsaturated fatty acid levels is negatively correlated with the incidence of stroke (OR = 0.800, 95% CI = 0.642–0.996, P value = 0.046), and docosahexaenoic acid levels is negatively correlated with the incidence of peripheral artery disease (OR = 0.747, 95% CI = 0.572–0.976, P value = 0.033). All results showed no heterogeneity or pleiotropy, but leave-one-out tests showed that the analysis results of some fatty acids were driven by a single SNP. This study highlights the existence of causal relationships between fatty acids and atherosclerotic diseases at the genetic level. These findings provide valuable insights for potential prevention measures and therapeutic targets for the three atherosclerotic diseases.