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

• Published in: Nutrients 2019-12, Vol.11 (12), p.3001
• Main Authors: Yuan, Shuai, Bäck, Magnus, Bruzelius, Maria, Mason, Amy M, Burgess, Stephen, Larsson, Susanna
• Format: Article
• Language: English
• Subjects: Alleles; alpha-Linolenic Acid - blood; Aortic valve; Arachidonic Acid - blood; Atherosclerosis; Cardiovascular disease; Cardiovascular diseases; Cardiovascular Diseases - blood; Cardiovascular Diseases - classification; Cardiovascular Diseases - genetics; Consortia; Coronary artery; Coronary artery disease; Coronary vessels; Data Analysis; Delta 5-desaturase; Delta-5 Fatty Acid Desaturase; Desaturase; diet; FADS; Fatty Acid Desaturases - genetics; Fatty acids; Fatty Acids - blood; Fibrillation; Gene expression; Genetic Predisposition to Disease; Genomes; Health risk assessment; Health risks; Heart diseases; Humans; Ischemia; Levels; Linoleic Acid - blood; Medicin och hälsovetenskap; Medicine; Mendelian randomisation; Mendelian Randomization Analysis; Metabolism; Nucleotides; Odds Ratio; Oleic acid; Oleic Acid - blood; Phospholipids; Phospholipids - blood; Polymorphism, Single Nucleotide; Protective Factors; Randomization; Risk Factors; Secondary analysis; Single-nucleotide polymorphism; Stearic acid; Stearic Acids - blood; Stenosis; Stroke; Thromboembolism
• ISSN: 2072-6643; 2072-6643
• DOI: 10.3390/nu11123001

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 gene were associated with most FAs. We performed a secondary analysis of the association between a functional variant (rs174547) in , 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 . In the secondary analysis, the minor allele of rs174547 in 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 , which was also associated with other CVDs.