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Plasma Phospholipid Fatty Acids, FADS1 and Risk of 15 Cardiovascular Diseases: A Mendelian Randomisation Study
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences. Karolinska Inst, Inst Environm Med, Unit Cardiovasc & Nutr Epidemiol, SE-17177 Stockholm, Sweden.ORCID iD: 0000-0001-5055-5627
Karolinska Inst, Dept Med, Ctr Mol Med, SE-17176 Stockholm, Sweden;Karolinska Univ Hosp, Div Valvular & Coronary Dis, Heart & Vasc Theme, SE-17176 Stockholm, Sweden.ORCID iD: 0000-0003-0853-5141
Karolinska Univ Hosp, Dept Hematol, Coagulat Unit, SE-17176 Stockholm, Sweden;Karolinska Inst, Dept Med Solna, SE-17176 Stockholm, Sweden.
Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge CB1 8RN, England.ORCID iD: 0000-0002-8019-0777
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2019 (English)In: Nutrients, ISSN 2072-6643, E-ISSN 2072-6643, Vol. 11, no 12, article id 3001Article in journal (Refereed) Published
Abstract [en]

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 CARDIoGRAMp1usC4D, 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 Delta 5-desaturase (a key enzyme in the endogenous FA synthesis), and CVD. Genetic predisposition to higher plasma alpha-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 alpha-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.

Place, publisher, year, edition, pages
MDPI , 2019. Vol. 11, no 12, article id 3001
Keywords [en]
cardiovascular disease, Delta 5-desaturase, diet, FADS, fatty acids, Mendelian randomisation
National Category
Cardiac and Cardiovascular Systems Nutrition and Dietetics
Identifiers
URN: urn:nbn:se:uu:diva-405334DOI: 10.3390/nu11123001ISI: 000506917800163PubMedID: 31817859OAI: oai:DiVA.org:uu-405334DiVA, id: diva2:1411582
Funder
Forte, Swedish Research Council for Health, Working Life and Welfare, 2018-00123Swedish Research Council, 2019-00977Wellcome trust, 204623/Z/16/ZAvailable from: 2020-03-04 Created: 2020-03-04 Last updated: 2020-03-04Bibliographically approved

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Yuan, ShuaiLarsson, Susanna C.

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