Circulating cytokines levels and osteoarthritis: A Mendelian randomization study.

BACKGROUND: Previous traditional observational studies have suggested the contribution of several cytokines and growth factors to the development of osteoarthritis (OA). This study aimed to determine the association of circulating cytokine and growth factor levels with OA. METHODS: We used two-sample Mendelian randomization (MR) to explore the causality between circulating cytokine and growth factor levels and OA [including knee or hip OA (K/HOA), knee OA (KOA), and hip OA (HOA)]. Summary level data for circulating cytokine and growth factor levels were sourced from a genome-wide association study (GWAS) involving 8,293 participants of Finnish ancestry. Single-nucleotide polymorphisms related to K/HOA (39,427 cases and 378,169 controls), KOA (24,955 cases and 378,169 controls), and HOA (15,704 cases and 378,169 controls) were obtained from a previous GWAS. The inverse variance weighted (IVW) method was primarily used for our MR analysis. For exposures to only one relevant SNP as IV, we used the Wald ratio as the major method to assess causal effects. We also conducted a series of sensitivity analyses to improve the robustness of the results. RESULTS: Circulating vascular endothelial growth factor levels were suggestively associated with an increased risk of K/HOA (odds ratio (OR) = 1.034; 95 % confidence interval (CI) = 1.013-1.055; P = 0.001), KOA (OR = 1.034; 95 % CI = 1.014-1.065; P = 0.002), and HOA (OR = 1.039; 95 % CI = 1.003-1.067; P = 0.034). Circulating interleukin (IL)-12p70 levels was suggestively associated with K/HOA (OR = 1.047; 95 % CI = 1.018-1.077; P = 0.001), KOA (OR = 1.058; 95 % CI = 1.022-1.095; P = 0.001), and HOA (OR = 1.044; 95 % CI = 1.000-1.091; P = 0.048). Circulating IL-18 levels were suggestively associated with HOA (OR = 1.068; 95 % CI = 1.014-1.125; P = 0.012). However, limited evidence exists to support causal genetic relationships between other circulating cytokines, growth factor levels and K/HOA, KOA, and HOA. CONCLUSIONS: Our MR analysis provides suggestive evidence of causal relationships between circulating cytokines and growth factors levels and OA, providing new insights into the etiology of OA.

Iron, copper, zinc and magnesium on rheumatoid arthritis: a two-sample Mendelian randomization study.

This study aimed to elucidate the causal genetic relationships between iron, copper, zinc, magnesium, and rheumatoid arthritis (RA). A two-sample Mendelian randomization (MR) analysis was conducted using the "TwoSampleMR" and "MendelianRandomization" packages in R. The random-effects inverse variance-weighted (IVW) method was used as the primary approach. We performed sensitivity analyses to test the reliability of the results. The random-effects IVW analysis revealed that there was no genetic causal relationship between iron (P = 0.429, odds ratio [OR] 95% confidence interval [CI] = 0.919 [0.746-1.133]), copper (P = 0.313, OR 95% CI = 0.973 [0.921-1.027]), zinc (P = 0.633, OR 95% CI = 0.978 [0.891-1.073]), or magnesium (P = 0.218, OR 95% CI = 0.792 [0.546-1.148]) and RA. Sensitivity analysis verified the reliability of the results. Therefore, there is no evidence to support a causal relationship between iron, copper, zinc, and magnesium intake at the genetic level and the development of RA.