Abstract
BackgroundAccumulating evidence has demonstrated the associations of omega-3 or omega-6 polyunsaturated fatty acids (PUFAs) with the disease activity and inflammatory mediators of systemic lupus erythematosus (SLE), but the evidence of causal links of omega-3 or omega-6 PUFAs on the risk for SLE remains inconclusive.ObjectivesThis study was conducted to evaluate the causal relationships between omega-3/omega-6 PUFAs and SLE by performing the Mendelian randomization (MR) analysis.MethodsGenome-wide significant single-nucleotide polymorphisms (SNPs) were obtained from genome-wide association studies (GWASs) of circulating omega-3/omega-6 levels (n = up to 13,544) and GWAS meta-analyses of SLE (n = 14,267), respectively. The bidirectional two-sample MR (TSMR) analysis was conducted to infer the causality.ResultsThe inverse-variance weighted (IVW) method revealed that genetically determined per SD increase in omega-3 levels were causally associated with an increased risk for SLE (odds ratios [ORs] = 1.49, 95% CI: 1.07, 2.08, p = 0.021), but no causal effect of omega-6 on the risk SLE was observed (IVW OR = 1.06, 95% CI: 0.72, 1.57, p = 0.759). In addition, there were no significantly causal associations in genetic predisposition to SLE with the changes of omega-3 and omega-6 levels, respectively (IVW beta for omega-3: 0.007, 95% CI: −0.006, 0.022, p = 0.299; IVW beta for omega-6: −0.008, 95% CI: −0.023, 0.006, p = 0.255).ConclusionThe present study revealed the possible causal role of omega-3 on increasing the risk for SLE, it could be the potential implications for dietary recommendations.
Highlights
Systemic lupus erythematosus (SLE) is an autoimmune inflammatory connective tissue disease involving multiple organs and tissues that are characterized as the loss of immune tolerance and immune-complex deposition [1, 2]
The results of inverse-variance weighted (IVW) method indicated that genetically determined per SD increase in omega-3 showed positive association with disease risk for SLE, with the odds ratio (OR) of 1.49 (Figure 2A and Table 1), the weighted median method yielded the consistent results (OR = 1.61, 95% CI: 1.14, 2.26, p = 0.007) (Table 1)
The results of MR analysis revealed that the genetically determined per SD increase of circulating omega-3 levels were causally associated with an increased disease risk for SLE
Summary
Systemic lupus erythematosus (SLE) is an autoimmune inflammatory connective tissue disease involving multiple organs and tissues that are characterized as the loss of immune tolerance and immune-complex deposition [1, 2]. Increasing evidence has demonstrated that the disease onset of SLE was triggered by the interactions of genetic susceptibility and several environmental factors [3,4,5]. Despite the implementation of many large-scale genome wide association studies (GWASs) with SLE, a better understanding of the causal roles of genetic susceptible loci would be helpful for the treatment and prevention of SLE. Evidence from human and animal studies indicated that omega-3 PUFAs, especially eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have anti-inflammation properties that showed some improvements in the rheumatic diseases [12,13,14]. Accumulating evidence has demonstrated the associations of omega-3 or omega-6 polyunsaturated fatty acids (PUFAs) with the disease activity and inflammatory mediators of systemic lupus erythematosus (SLE), but the evidence of causal links of omega-3 or omega-6 PUFAs on the risk for SLE remains inconclusive
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