Exploring the causal effect of omega-3 polyunsaturated fatty acid levels on the risk of type 1 diabetes: a Mendelian randomization study

Abstract

The burden of Type 1 diabetes (T1D) is vast and as of 2021, an estimated 8.4 million people were living with the disease worldwide. Predictably, this number could increase to 17.4 million people by 2040. Despite nearly a century of insulin therapy for the management of hyperglycemia in T1D, no therapies exist to treat its underlying etiopathology. Adequate dietary intake of omega-3 fatty acids (ω-3) has been reported in observational studies and Randomized Controlled Trials to be associated with reduced risk of developing T1D but results have been inconclusive. We conducted a Mendelian randomization (MR) study to explore the relationship between ω-3 intake and T1D. We performed a two-sample MR analysis using single nucleotide polymorphisms associated with ω-3 levels in a sample of 114,999 Europeans and their effects on T1D from a genome-wide association study meta-analysis of 24,840 European participants. A main MR analysis using the Inverse-variance weighted (IVW) method was conducted and validated using MR-Egger, Weighted median, and Weighted mode methods. Sensitivity analyses excluding potentially pleiotropic single nucleotide polymorphisms were also performed. Main MR analysis using the IVW method showed no evidence of a causal relationship between ω-3 levels and T1D risk (OR: 0.92, 95% CI: 0.56–1.51, p = 0.745). MR-Egger and Weighted mode methods showed similar results while Weighted median showed a marginally significant association (OR: 1.15, CI: 1.00–1.32, p = 0.048). Sensitivity analysis revealed heterogeneity in the main analysis MR estimates (IVW Q > 100, p < 0.0001) and no directional pleiotropy (Egger intercept: −0.032, p = 0.261). Our study found limited evidence of a causal association between ω-3 and T1D, with only a marginally significant association observed in one of the four MR methods. This challenges the proposition that ω-3-rich diets are of substantial benefit for the prevention and management of T1D.