Heterogenous causal effects of serum fatty acid levels on the risk of cerebral and abdominal aortic aneurysm: a Mendelian Randomization study

The presence of aneurysms, encompassing cerebral and abdominal aortic aneurysms, poses significant risks to individuals' health. The serum fatty acids (FAs) are implicated in various diseases, yet their causal association with different aneurysms remain less understood. In this study, the summary-level datasets associated with FAs and cerebral and abdominal aortic aneurysms from the UK Biobank and BioBank Japan were included. Two-sample Mendelian randomization (MR) analysis, replicated and reverse MR analysis were conducted to explore the causal association between serum FA levels with both cerebral aneurysm (CA) and abdominal aortic aneurysm (AA). The inverse variance weighting (IVW) was used as the primary method, together with sensitivity analyses for pleiotropy and heterogenous tests. As a result, the ratio of omega-6 FAs to omega-3 FAs serves as a detrimental effector of CA, and ratio of docosahexaenoic acid to total FA levels, omega-3 FA levels and ratio of omega-3 FAs to total FAs are beneficial effectors. Counterintuitively, monounsaturated FAs (MUFAs), ratio of MUFAs to total FAs, and omega-6 FAs serve as detrimental effectors of AA. Collectively, these results suggest novel serum FA levels of causal association with CA and AA, and shed light upon the distinct molecular underpinnings of the two types of aneurysms.