Genetic analysis of comorbidities between osteoarthritis, sarcopenia, and osteoporosis

作者：Zhi Liu, Xiangming Chen, Zhe Ruan, Chao Wang, Dongliang Yuan, Wenfeng Xiao, Yusheng Li, Shushan Zhao · 发表于：Experimental Gerontology · 年份：2025 · DOI：10.1016/j.exger.2025.112788 · 被引用次数：5 · 研究领域：Bone health and osteoporosis research、Genetic Associations and Epidemiology、Osteoarthritis Treatment and Mechanisms

BACKGROUND: Osteoarthritis (OA), sarcopenia (SCP), and osteoporosis (OP) pose a substantial global morbidity and mortality burden, and previous studies have observed potential associations among them. This study aims to comprehensively characterize the common genetic structure, biological basis, and underlying causal relationship among OA, SCP, and OP. METHODS: We used pooled statistics from the largest European genome-wide association study to investigate the genetic overlap and underlying causal relationships among OA, SCP, and OP. LD Score Regression (LDSC) was first used for estimating global and local genetic associations, cross-trait meta-analysis was then conducted to identify shared loci, and mendelian randomization (MR) analysis was performed to test causal association. RESULTS: In global and local genetic correlation analysis, we found strong positive correlations among OA, SCP, and OP. Cross-trait meta-analysis revealed 9 novel pleiotropic loci for HandOA_SCP trait-pairs, 1 for ThumbOA_SCP (females), and 6 for KneeOA_SCP (males)0.10 novel pleiotropic loci were also identified for HipOA_TBMD, while none for WLM_FinOP. Bidirectional MR analyses indicated significant causal associations between HandOA and SCP(Forward: OR: 1.41, 95 % CI: 1.25-1.60, p < 0.01,Reverse: OR: 1.77, 95 % CI: 1.34-2.35, p < 0.01). Reverse analyses suggested that ThumbOA.female (OR: 1.92, 95 % CI:1.18-3.13, p < 0.01) and KneeOA.male (OR: 1.58, 95 % CI: 1.13-2.12, p < 0.01) were positively corre...