Abstract
BackgroundThe cardioprotective ability of n-3 polyunsaturated fatty acids (PUFAs) is controversial. Most studies suggest a specific role for PUFAs in cardioprotection from ischemic heart disease (IHD). However, few studies have used genetic biomarkers of n-3 PUFAs to examine their potential relationships with IHD. This study aimed to use Mendelian randomization to evaluate whether genetically-predicted n-3 PUFAs affect IHD and cardiometabolic risk factors (CRFs).MethodsGenetic variants strongly (p < 5 × 10–8) and independently (r2 > 0.1) associated with n-3 PUFAs were derived from the CHARGE Consortium (including 8,866 subjects of European ancestry) and were used as instrumental variables (IVs) for evaluating the effect of n-3 PUFAs, including α-linolenic acid (ALA), docosapentaenoic acid (DPA), docosahexaenoic acid (DHA), and eicosapentaenoic acid (EPA). Data on the associations between the IVs and IHD, myocardial infarction, and CRFs (including diabetes, lipids, blood pressure, body mass index, and waist-to-hip ratio (WHR)) were obtained from the UK Biobank SOFT CAD GWAS with the CARDIoGRAMplusC4D 1000 Genomes-based GWAS (113,937 IHD cases and 339,115 controls), the Myocardial Infarction Genetics and CARDIoGRAM Exome consortia (42,335 MI cases and 78,240 controls), the DIAbetes Genetics Replication And Meta-analysis consortium (26,676 diabetes mellitus cases and 132,532 controls), the Global Lipids Genetics Consortium (n = 196,475), the International Consortium for Blood Pressure (n = 69,395), and the meta-analysis of GWAS for body fat distribution in the UK Biobank and Genetic Investigation of Anthropometric Traits (n = 694,649).ResultsGenetically-predicted higher ALA was associated with lower risk of IHD, type 2 diabetes (T2D), and lower serum lipids. The effect size per 0.05-unit increase (about 1 standard deviation) in plasma ALA level) was − 1.173 (95% confidence interval − 2.214 to − 0.133) for IHD. DPA and EPA had no association with IHD but were associated with a higher risk of T2D, higher levels of lipids or WHR. DHA had no association with IHD or CRFs.ConclusionsOur study suggests a benefit of ALA for IHD and its main risk factors. DHA, DPA, and EPA had no association with IHD but were partly associated with increasing cardiometabolic risk factors.
Highlights
The cardioprotective ability of n-3 polyunsaturated fatty acids (PUFAs) is controversial
Genetic associations with ischemic heart disease (IHD), type 2 diabetes (T2D), lipids, blood pressure, body mass index (BMI), and waist‐to‐hip ratio (WHR) Genetic associations with IHD were obtained from the published meta-analysis of UK Biobank SOFT CAD genome-wide association studies (GWAS) with the CARDIoGRAMplusC4D 1000 Genomes-based GWAS and the Myocardial Infarction Genetics and CARDIoGRAM Exome, which is the most up-to-date GWAS of IHD applied to the UK Biobank and involved 113,937 IHD cases and 339,115 controls in total
Three Single nucleotide polymorphism (SNP) were associated with high-density lipoprotein (HDL), three SNPs were associated with total cholesterol (TC), four SNPs were associated with TG, and one SNP was associated with BMI
Summary
The cardioprotective ability of n-3 polyunsaturated fatty acids (PUFAs) is controversial. N-3 polyunsaturated fatty acids (PUFAs) include plantderived α-linolenic acid (ALA) and marine-derived docosahexaenoic acid (DHA), docosapentaenoic acid (DPA), and eicosapentaenoic acid (EPA). The nutrition recommendations for n-3 PUFA supplements or seafood for cardiovascular benefits have been debated in recent years, but without consensus being reached [10]. These controversies may be confounded by background dietary consumption of fish, health status, medical treatment of IHD, socioeconomic position, lifestyle, different study populations, and different definitions of CVD and study endpoints [1, 10]
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