Chinese Journal of Tissue Engineering Research ›› 2026, Vol. 30 ›› Issue (18): 4763-4770.doi: 10.12307/2026.741

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

Yu Yueyue1, 2, Zhang Xu2, Liu Yiwei2, Meng Zihan2, Hao Xinyue3, Tian Chunyu2, 4, Li Ji’an2, 4, Zhang Yixin1    

  1. 1Hebei University of Chinese Medicine, Shijiazhuang 050200, Hebei Province, China; 2North China University of Science and Technology, Tangshan 063210, Hebei Province, China; 3Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China; 4Hebei Key Laboratory of Integrated Traditional Chinese and Western Medicine for Diabetes and Its Complications, Tangshan 063210, Hebei Province, China
  • Received:2025-07-09 Accepted:2025-09-16 Online:2026-06-28 Published:2025-12-11
  • Contact: Zhang Yixin, Professor, Hebei University of Chinese Medicine, Shijiazhuang 050200, Hebei Province, China Co-corresponding author: Li Ji’an, Professor, North China University of Science and Technology, Tangshan 063210, Hebei Province, China; Hebei Key Laboratory of Integrated Traditional Chinese and Western Medicine for Diabetes and Its Complications, Tangshan 063210, Hebei Province, China
  • About author:Yu Yueyue, PhD candidate, Associate professor, Hebei University of Chinese Medicine, Shijiazhuang 050200, Hebei Province, China; North China University of Science and Technology, Tangshan 063210, Hebei Province, China
  • Supported by:
    Science and Technology Assistance Program for Developing Countries, Ministry of Science and Technology of China, No. KY01904005 (to LJA); Hebei Provincial International Cooperation Special Project, No. 19392507D (to LJA); Hebei Provincial Basic Research Fund for Provincial Universities, North China University of Technology, No. JQN2021034 (to YYY)

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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. 


Key words: knee osteoarthritis, lipid types, Mendelian randomization, genetic variation, causal relationship, diacylglycerol, phosphatidylinositol, phosphatidylcholine

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