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Nutrients. 2019 Dec 7;11(12). pii: E3001. doi: 10.3390/nu11123001.

Plasma Phospholipid Fatty Acids, FADS1 and Risk of 15 Cardiovascular Diseases: A Mendelian Randomisation Study.

Author information

1
Unit of Cardiovascular and Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, SE-171 77 Stockholm, Sweden.
2
Department of Surgical Sciences, Uppsala University, SE-751 85 Uppsala, Sweden.
3
Department of Medicine, Center for Molecular Medicine, Karolinska Institutet, SE-171 76 Stockholm, Sweden.
4
Heart and Vascular Theme-Division of Valvular and Coronary Disease, Karolinska University Hospital, SE-171 76 Stockholm, Sweden.
5
Coagulation Unit, Department of Hematology, Karolinska University Hospital, SE-171 76 Stockholm, Sweden.
6
Department of Medicine Solna, Karolinska Institutet, SE-171 76 Stockholm, Sweden.
7
Department of Public Health and Primary Care, University of Cambridge, CB1 8RN Cambridge, UK.
8
MRC Biostatistics Unit, University of Cambridge, CB2 0SR Cambridge, UK.

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 ?5-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.

KEYWORDS:

?5-desaturase; FADS; Mendelian randomisation; cardiovascular disease; diet; fatty acids

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