AUTHOR=Su Dalin , Ai Yanhong , Zhu Guoyong , Yang Yubiao , Ma Pengyi 

TITLE=Genetically predicted circulating levels of cytokines and the risk of osteoarthritis: A mendelian randomization study

JOURNAL=Frontiers in Genetics

VOLUME=Volume 14 - 2023

YEAR=2023

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2023.1131198

DOI=10.3389/fgene.2023.1131198

ISSN=1664-8021

ABSTRACT=The association between inflammatory cytokines and osteoarthritis (OA) has been reported in several observational studies, but the causal relationship between the two remains unknown. Hence, we performed this two-sample Mendelian randomization (MR) to confirm the causal relationship between circulating levels of inflammatory factors and osteoarthritis risk. We used genetic variants associated with cytokine circulation levels from a meta-analysis of genome-wide association studies (GWASs) in 8,293 Finns as instrumental variables and obtain OA data from the UK Biobank, including a total of 345,169 subjects of European ancestry (66,031 diagnosed OA cases and 279,138 controls). Inverse variance weighting (IVW), MR-Egger, Wald Ratio, weighted median, and MR multiplicxity residual sums with outliers (MR-PRESSO) were used.We found a causal relationship between circulating levels of macrophage inflammatory protein-1beta (MIP-1) and risk of OA (OR=0.998, 95% CI=0.996-0.999, P=9.6110-5); tumor necrosis factor beta (TNF-) was also causally associated with risk of OA (OR= 0.996,95%CI=0.994-0.999, P=0.002); finally we found a suggestive association between C-C motif chemokine ligand 5(CCL5, also called Rantes) and OA risk (OR=1.013, 95%CI= 1.002-1.024, P=0.016). Our study systematically assessed the role of inflammatory cytokines among OA through a genetic epidemiological approach. It provides new insights into the pathogenesis of OA and also provides potential therapeutic targets for the treatment of OA.