Evaluating the distinct pleiotropic effects of omega-3 fatty acids on type 2 diabetes mellitus: a mendelian randomization study
Abstract
Background Observational studies and conventional Mendelian randomization (MR) studies showed inconclusive evidence to support the association between omega-3 fatty acids and type 2 diabetes. We aim to evaluate the causal effect of omega-3 fatty acids on type 2 diabetes mellitus (T2DM), and the distinct intermediate phenotypes linking the two. Methods Two-sample MR was performed using genetic instruments derived from a recent genome-wide association study (GWAS) of omega-3 fatty acids (N = 114,999) from UK Biobank and outcome data obtained from a large-scale T2DM GWAS (62,892 cases and 596,424 controls) in European ancestry. MR-Clust was applied to determine clustered genetic instruments of omega-3 fatty acids that influences T2DM. Two-step MR analysis was used to identify potential intermediate phenotypes (e.g. glycemic traits) that linking omega-3 fatty acids with T2DM. Results Univariate MR showed heterogenous effect of omega-3 fatty acids on T2DM. At least two pleiotropic effects between omega-3 fatty acids and T2DM were identified using MR-Clust. For cluster 1 with seven instruments, increasing omega-3 fatty acids reduced T2DM risk (OR: 0.52, 95%CI 0.45–0.59), and decreased HOMA-IR (β = − 0.13, SE = 0.05, P = 0.02). On the contrary, MR analysis using 10 instruments in cluster 2 showed that increasing omega-3 fatty acids increased T2DM risk (OR:1.10; 95%CI 1.06–1.15), and decreased HOMA-B (β = − 0.04, SE = 0.01, P = 4.52 × 10^–5). Two-step MR indicated that increasing…
Read the paper
Related studies
- Promising Sources of Plant-Derived Polyunsaturated Fatty Acids: A Narrative Review
- Effects of omega-3 polyunsaturated fatty acid intake in patients with chronic kidney disease: Systematic review and meta-analysis of randomized controlled trials
- Effect of omega-3 fatty acids on cognition: an updated systematic review of randomized clinical trials
- The role of omega-3 polyunsaturated fatty acid supplementation in the management of type 2 diabetes mellitus: A narrative review
- Paucity of evidence for a relationship between long-chain omega-3 fatty acid intake and chronic obstructive pulmonary disease: a systematic review
- Omega-3 fatty acid nanocarriers: Characterization and potential applications
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.