Causal Effects of Serum Levels of n-3 or n-6 Polyunsaturated Fatty Acids on Coronary Artery Disease: Mendelian Randomization Study

• Published in: Nutrients Vol. 13; no. 5; p. 1490
• Main Authors: Park, Sehoon, Lee, Soojin, Kim, Yaerim, Lee, Yeonhee, Kang, Minwoo, Kim, Kwangsoo, Kim, Yongchul, Han, Seungseok, Lee, Hajeong, Lee, Jungpyo, Joo, Kwonwook, Lim, Chunsoo, Kim, Yonsu, Kim, Dongki
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 28.04.2021; MDPI
• Subjects: Alleles; Analysis; Arachidonic acid; Biobanks; Cardiovascular disease; Cohort Studies; Coronary artery; Coronary artery disease; Coronary Artery Disease - blood; Coronary heart disease; Coronary vessels; Diabetes; Disease prevention; Eicosapentaenoic acid; Essential fatty acids; Fatty acids; Fatty Acids, Omega-3 - blood; Fatty Acids, Omega-6 - blood; Female; Genome-wide association studies; Genomes; Genomics; Health risks; Heart diseases; Humans; Hypertension; Linoleic acid; Linolenic acid; Lipoproteins; Male; Medical research; Medicine, Experimental; mendelian randomization; Mendelian Randomization Analysis - methods; Metabolic disorders; Middle Aged; myocardial infarction; Pleiotropy; polyunsaturated fatty acids; Randomization; Risk; risk factor; Sensitivity analysis; Serum levels; Triglycerides; United Kingdom; Unsaturated fatty acids; United Kingdom; South Korea; United Kingdom > UK; coronary artery disease; risk factor; mendelian randomization; myocardial infarction; polyunsaturated fatty acids
• ISSN: 2072-6643; 2072-6643
• DOI: 10.3390/nu13051490

We aimed to investigate the causal effects of n-3 and n-6 polyunsaturated fatty acids (PUFAs) on the risk of coronary artery disease (CAD) through Mendelian randomization (MR) analysis. This MR study utilized a genetic instrument developed from previous genome-wide association studies for various serum n-3 and n-6 PUFA levels. First, we calculated the allele scores for genetic predisposition of PUFAs in individuals of European ancestry in the UK Biobank data ( = 337,129). The allele score-based MR was obtained by regressing the allele scores to CAD risks. Second, summary-level MR was performed with the CARDIoGRAMplusC4D data for CAD ( = 184,305). Higher genetically predicted eicosapentaenoic acid and dihomo-gamma-linolenic acid levels were significantly associated with a lower risk of CAD both in the allele-score-based and summary-level MR analyses. Higher allele scores for linoleic acid level were significantly associated with lower CAD risks, and in the summary-level MR, the causal estimates by the pleiotropy-robust MR methods also indicated that higher linoleic acid levels cause a lower risk of CAD. Arachidonic acid showed significant causal estimates for a higher risk of CAD. This study supports the causal effects of certain n-3 and n-6 PUFA types on the risk of CAD.