Mendelian randomization of plasma lipidome and temporomandibular joint disorders

Abstract

Mendelian randomization (MR) was used to investigate the possible causal association between lipids (LP) and temporomandibular joint disorders (TMD). To investigate the causal relationship between circulating LP and TMD, we conducted a 2-sample MR analysis. Exposure data comprised summary statistics for 179 LP from the GeneRISK genome-wide association study (N = 7174 samples). Outcome data were derived from the FinnGen genome-wide association study for TMD (N = 185169 samples). Primary causal estimates were generated using inverse-variance weighted regression, with sensitivity analyses including MR-Egger, weighted median, and Mendelian Randomization Pleiotropy RESidual Sum and Outlier. Robustness was assessed through pleiotropy-robust methods, heterogeneity testing, and leave-one-out analysis. Our analysis identified specific lipid species associated with temporomandibular joint disorder risk. Diacylglycerol (18:1_18:1) (odds ratio [OR] = 1.067, 95% confidence interval [CI] = 1.016−1.121, P = .010) and several triacylglycerols (TGs) were significantly associated with increased risk: TG (50:3) (OR = 1.053, 95% CI = 1.006–1.102, P = .028), TG (52:3) (OR = 1.073, 95% CI = 1.031–1.118, P = .001), TG (53:3) (OR = 1.062, 95% CI = 1.017–1.109, P = .006), TG (56:5) (OR = 1.057, 95% CI = 1.005–1.111, P = .032), and TG (56:6) (OR = 1.066, 95% CI = 1.020–1.114, P = .004). In contrast, Phosphatidylcholine (15:0_18:2) (OR = 0.953, 95% CI = 0.920–0.987, P = .007) and Phosphatidylcholine (16:0_18:2) (OR = 0.961, 95% CI = 0.928–0.996, P = .031) were associated with a reduced risk. Our MR analysis provides evidence supporting a putative causal relationship between specific plasma lipid species and the development of TMD. These findings highlight the potential role of lipid metabolism in TMD pathogenesis and warrant further investigation.