Lipid types and knee osteoarthritis:a genome-wide association study in European populations

Yu Yueyue; Zhang Xu; Liu Yiwei; Meng Zihan; Hao Xinyue; Tian Chunyu; Li Ji'an; Zhang Yixin

doi:10.12307/2026.741

Abstract：BACKGROUND:Studies have shown that different lipid types can affect knee osteoarthritis,but the causal relationship remains unclear. OBJECTIVE:To explore the causal relationship between lipid types and knee osteoarthritis using Mendelian randomization. METHODS:Based on the genome-wide association analysis statistics from the GWAS Catalog,179 types of lipids were derived from the GeneRISK cohort,and whole genome analysis data for knee osteoarthritis included 2 227 cases and 454 121 controls.Single nucleotide polymorphisms were used as instrumental variables and a strict screening was conducted with a liposome significance threshold of P<1×10⁻⁵,a knee osteoarthritis significance threshold of P<5×10-6 and a linkage disequilibrium threshold of r²<0.001.The inverse variance weighted method was mainly used for analysis.The results were evaluated based on the odds ratio(OR)and its 95%confidence interval(CI).MR-Egger regression,weighted median method,and simple mode method were used as supplementary analyses.The robustness of the results was verified through sensitivity analyses including leave-one-out analysis,heterogeneity test,pleiotropy test,and reverse Mendelian randomization analysis. RESULTS AND CONCLUSION:Diacylglycerol(18:1/18:2,OR=0.900 5,95%CI:0.810 9-1.000 0,P=0.049 9),phosphatidylinositol(18:0/18:2,OR=0.895 4,95%CI:0.808 9-0.991 2,P=0.033 2),and phosphatidylcholine(16:0/20:2,OR=0.918 3,95%CI:0.845 8-0.997 1,P=0.042 5)were negatively correlated with knee osteoarthritis,while phosphatidylcholine(O-16:0/18:2,OR=1.221 9,95%CI:0.909 8-1.641 0,P=0.198 7)was positively correlated with knee osteoarthritis.To conclude,specific lipids may influence the risk of knee osteoarthritis by regulating inflammatory or cartilage metabolic pathways,providing genetic evidence for lipid metabolism-targeted intervention strategies.