Abstract
Whether circulating fatty acids (FAs) play a causal role in the development of cardiovascular disease (CVD) remains unclear. We conducted a Mendelian randomisation study to explore the associations between plasma phospholipid FA levels and 15 CVDs. Summary-level data from the CARDIoGRAMplusC4D, MEGASTROKE, and Atrial Fibrillation consortia and UK Biobank were used. Sixteen single-nucleotide polymorphisms (SNPs) associated with ten plasma FAs were used as instrumental variables. SNPs in or close to the FADS1 gene were associated with most FAs. We performed a secondary analysis of the association between a functional variant (rs174547) in FADS1, which encodes 𝛥5-desaturase (a key enzyme in the endogenous FA synthesis), and CVD. Genetic predisposition to higher plasma α-linolenic, linoleic, and oleic acid levels was associated with lower odds of large-artery stroke and venous thromboembolism, whereas higher arachidonic and stearic acid levels were associated with higher odds of these two CVDs. The associations were driven by SNPs in or close to FADS1. In the secondary analysis, the minor allele of rs174547 in FADS1 was associated with significantly lower odds of any ischemic stroke, large-artery stroke, and venous thromboembolism and showed suggestive evidence of inverse association with coronary artery disease, abdominal aortic aneurysm and aortic valve stenosis. Genetically higher plasma α-linolenic, linoleic, and oleic acid levels are inversely associated with large-artery stroke and venous thromboembolism, whereas arachidonic and stearic acid levels are positively associated with these CVDs. The associations were driven by FADS1, which was also associated with other CVDs.
Highlights
Cardiovascular disease (CVD) is one of the leading causes of mortality and disability among men and women worldwide [1,2]
The associations were driven by FADS1, which was associated with other CVDs
Genetic predisposition to higher plasma levels of α-linolenic acid (ALA), linoleic acid (LA), and oleic acid (OA) was in Table 1 and Figure 2
Summary
Cardiovascular disease (CVD) is one of the leading causes of mortality and disability among men and women worldwide [1,2]. Cardiovascular disease (CVD) is one of the leading causes of mortality and disability among men and womentoworldwide. Fatty acidsrisk (FAs)factor, suboptimal diet is an important preventable risk factor [3]. Among dietary the types consumed have been considered to play an important role infor theCVD prevention of CVD [4]. Factors, It has been of fatty (FAs)intake consumed have beenFAs, considered to play an important role the prevention proposed thatacids increased of unsaturated polyunsaturated fattyinacids (PUFA), of CVD [4]. Will decrease the incidence of CVD by lowering fatty acids (PUFA),cholesterol and decreased intake of saturated fattyimproving acids (SFA). Will decrease the[6], incidence of low-density lipoprotein and triglyceride levels [4,5,6], insulin sensitivity and CVDsystemic by lowering low-density cholesterol and triglyceride levels [4,5,6], insulin reducing inflammation [6].lipoprotein
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