ABSTRACT
Previous observational studies have suggested an important role of omega-3 in low back pain. In the present study, we used a two-sample Mendelian randomization (MR) study to identify the putative causal link between omega-3 and low back pain. A broadly used genome-wide association study (GWAS) (n = 8,866 individuals from European ancestry) was used to select plasma omega-3 genetic instrumental variables (IVs). A previously reported GWAS (4,863 cases and 74,589 controls from European ancestry) for low back pain were used to assess the effect of plasma omega-3 levels on low back pain. MR-egger_intercept, MR-PRESSO, MR_egger, and inverse variance weighted (IVW) in Cochran's Q-test were used to determine the pleiotropy and heterogeneity, respectively. MR-egger, weighted median, IVW, and weighted mode were used to perform MR analysis. Finally, the effect of a single nucleotide polymorphism (SNP) was used to test the SNP bias. We did not find a significant pleiotropy or heterogeneity of all six selected plasma omega-3 genetic IVs in low back pain GWAS. Expectedly, we found that as plasma omega-3 levels genetically increased, the risk of low back pain had a decreased trend using MR-egger (Beta = -0.593, p = 0.228; OR = 0.553) and weighted mode (Beta = -0.251, p = 0.281; OR = 0.778). This reduced trend was further proven by weighted median (Beta = -0.436, p = 0.025; OR = 0.646) and IVW (Beta = -0.366, p = 0.049; OR = 0.694). Our analysis suggested a putative causal link between genetically increased plasma omega-3 levels and the reduced risk of low back pain in European ancestries. Thus, the supplementation of omega-3 may be important for the prevention and treatment of low back pain.
ABSTRACT
OBJECTIVES: To resolve the ongoing debate on the role of plasma omega-3 fatty acids in rheumatoid arthritis (RA), we attempted to identify the association between omega-3 intake and the risk of RA. METHODS: We analyzed data from the largest genome-wide association study (GWAS) for omega-3 fatty acids (N = 114,999 of European ancestry) and RA (14,361 cases and 43,923 controls of European ancestry). Mendelian randomization-egger_intercept, MR-PRESSO, and Cochran's Q test were used to determine pleiotropy and heterogeneity. Egger, weighted median, inverse variance weighted (IVW), simple mode, and weighted mode were used to evaluate the causal association of plasma omega-3 levels on RA. RESULTS: We found no significant pleiotropy, heterogeneity, and bias among the omega-3 genetic instrumental variables (IVs) in RA GWAS datasets. MR analysis demonstrated that as omega-3 levels genetically increased, the risk of MS increased using MR-egger (Beta = 0.137, p = 0.037; OR = 1.146, 95% CI: [1.014, 1.296]), weighted median (Beta = 0.162, p = 0.001; OR = 1.176, 95% CI: [1.070, 1.292]), IVW (Beta = 0.102, p = 0.025; OR = 1.108, 95% CI: [1.013, 1.211]), simple mode (Beta = 0.219, p = 0.149; OR = 1.245, 95% CI: [0.931, 1.665]), and weighted mode (Beta = 0.146, p = 0.006; OR = 1.157, 95% CI: [1.051, 1.274]). CONCLUSIONS: Our analysis suggested a causal association between genetically increased plasma omega-3 levels and the increased risk of RA in populations with European ancestry. Thus, to reduce the risk of RA, those of European descent should reduce omega-3 intake. Key Points ⢠No significant pleiotropy or heterogeneity among the omega-3 genetic IVs in RA GWAS datasets. ⢠Genetically increased plasma omega-3 levels enhanced the risk of RA in European lineages.
Subject(s)
Arthritis, Rheumatoid , Fatty Acids, Omega-3 , Arthritis, Rheumatoid/genetics , Genome-Wide Association Study , Humans , Mendelian Randomization Analysis , Polymorphism, Single NucleotideABSTRACT
The interleukin (IL)12 family cytokines have been examined as therapeutic targets in the treatment of several autoimmune diseases. Our previous study showed that a novel IL12 family cytokine, IL39 (IL23p19/Ebi3) mediates inflammation in lupuslike mice. In the present study, the effect of antimouse IL39 polyclonal antibodies on autoimmune symptoms in lupuslike mice was investigated. Rabbit antimouse IL39 polyclonal antibodies were produced by immunization with recombinant mouse IL39, and purified using protein A chromatography. These antibodies were subsequently used to treat lupuslike mice. Flow cytometry, captured images, ELISA and H&E staining were used to determine the effect of antiIL39 polyclonal antibodies on inflammatory cells, autoantibody titers, proteinuria, infiltrating inflammatory cells and the structure of the glomerular region. The antiIL39 polyclonal antibodies effectively reduced the numbers of inflammatory cells, splenomegaly, autoantibody titers, proteinuria, infiltrating inflammatory cells, and restored the structure of the glomerular region in MRL/lpr mice. Taken together, these results suggested that antiIL39 polyclonal antibodies ameliorated autoimmune symptoms in lupuslike mice. Therefore, IL39 may be used as a possible target for the treatment of systemic lupus erythematosus.