Genetic analysis of comorbidities between osteoarthritis, sarcopenia, and osteoporosis
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...
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Elsevier
2025-07-01
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| Series: | Experimental Gerontology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0531556525001172 |
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| author | Zhi Liu XiangMing Chen Zhe Ruan Chao Wang Dongliang Yuan Wenfeng Xiao Yusheng Li Shushan Zhao |
| author_facet | Zhi Liu XiangMing Chen Zhe Ruan Chao Wang Dongliang Yuan Wenfeng Xiao Yusheng Li Shushan Zhao |
| author_sort | Zhi Liu |
| collection | DOAJ |
| description | 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 correlated with SCP, while TBMD was positively correlated with HipOA (OR: 1.23, 95 % CI: 1.16–1.31, p < 0.01). Conclusions: Our work demonstrates a shared genetic basis, pleiotropic loci, and putative causal relationships among OA, SCP, and OP, highlighting the intrinsic links behind these three complex skeletal diseases. |
| format | Article |
| id | doaj-art-700a992c97e046baaa522cac8b2317ca |
| institution | DOAJ |
| issn | 1873-6815 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Experimental Gerontology |
| spelling | doaj-art-700a992c97e046baaa522cac8b2317ca2025-08-20T03:12:39ZengElsevierExperimental Gerontology1873-68152025-07-0120611278810.1016/j.exger.2025.112788Genetic analysis of comorbidities between osteoarthritis, sarcopenia, and osteoporosisZhi Liu0XiangMing Chen1Zhe Ruan2Chao Wang3Dongliang Yuan4Wenfeng Xiao5Yusheng Li6Shushan Zhao7Department of Orthopaedics, Xiangya Hospital, Central South University, Changsha 410008, Hunan, PR China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan 410008, PR ChinaDepartment of Orthopaedics, Xiangya Hospital, Central South University, Changsha 410008, Hunan, PR China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan 410008, PR ChinaDepartment of Orthopaedics, The First Hospital of Changsha, Changsha 410005, PR China; The Affiliated Changsha Hospital of Xiangya School of Medicine, Central South University, Changsha 410008, PR ChinaDepartment of Orthopaedics, Xiangya Hospital, Central South University, Changsha 410008, Hunan, PR ChinaDepartment of Orthopaedics, Xiangya Hospital, Central South University, Changsha 410008, Hunan, PR ChinaDepartment of Orthopaedics, Xiangya Hospital, Central South University, Changsha 410008, Hunan, PR China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan 410008, PR ChinaDepartment of Orthopaedics, Xiangya Hospital, Central South University, Changsha 410008, Hunan, PR China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan 410008, PR ChinaDepartment of Orthopaedics, Xiangya Hospital, Central South University, Changsha 410008, Hunan, PR China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan 410008, PR China; Corresponding author at: Department of Orthopaedics, Xiangya Hospital, Central South University, Changsha 410008, Hunan, PR China.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 correlated with SCP, while TBMD was positively correlated with HipOA (OR: 1.23, 95 % CI: 1.16–1.31, p < 0.01). Conclusions: Our work demonstrates a shared genetic basis, pleiotropic loci, and putative causal relationships among OA, SCP, and OP, highlighting the intrinsic links behind these three complex skeletal diseases.http://www.sciencedirect.com/science/article/pii/S0531556525001172OsteoarthritisSarcopeniaOsteoporosisGenetic correlationShared genetic structureCausal association |
| spellingShingle | Zhi Liu XiangMing Chen Zhe Ruan Chao Wang Dongliang Yuan Wenfeng Xiao Yusheng Li Shushan Zhao Genetic analysis of comorbidities between osteoarthritis, sarcopenia, and osteoporosis Experimental Gerontology Osteoarthritis Sarcopenia Osteoporosis Genetic correlation Shared genetic structure Causal association |
| title | Genetic analysis of comorbidities between osteoarthritis, sarcopenia, and osteoporosis |
| title_full | Genetic analysis of comorbidities between osteoarthritis, sarcopenia, and osteoporosis |
| title_fullStr | Genetic analysis of comorbidities between osteoarthritis, sarcopenia, and osteoporosis |
| title_full_unstemmed | Genetic analysis of comorbidities between osteoarthritis, sarcopenia, and osteoporosis |
| title_short | Genetic analysis of comorbidities between osteoarthritis, sarcopenia, and osteoporosis |
| title_sort | genetic analysis of comorbidities between osteoarthritis sarcopenia and osteoporosis |
| topic | Osteoarthritis Sarcopenia Osteoporosis Genetic correlation Shared genetic structure Causal association |
| url | http://www.sciencedirect.com/science/article/pii/S0531556525001172 |
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