Causal associations between osteoporosis and HBV infection across Asian and European populations: evidence from Mendelian randomization and colocalization analysis
IntroductionClinical studies have demonstrated a potential association between chronic hepatitis caused by hepatitis B virus (HBV) infection and osteoporosis. However, the causal relationship between HBV infection and osteoporosis remains to be determined.MethodsWe investigated whether HBV infection...
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Frontiers Media S.A.
2025-01-01
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| author | Zhengnan Li Jiarui Cao Ke Li Yixin Wu Zhanpeng Luo Rui Cao Zhiheng Cheng Zhendong Tian Yiyang Han Yuping Lai Bangqi Wang Shen Chen |
| author_facet | Zhengnan Li Jiarui Cao Ke Li Yixin Wu Zhanpeng Luo Rui Cao Zhiheng Cheng Zhendong Tian Yiyang Han Yuping Lai Bangqi Wang Shen Chen |
| author_sort | Zhengnan Li |
| collection | DOAJ |
| description | IntroductionClinical studies have demonstrated a potential association between chronic hepatitis caused by hepatitis B virus (HBV) infection and osteoporosis. However, the causal relationship between HBV infection and osteoporosis remains to be determined.MethodsWe investigated whether HBV infection is causally associated with osteoporosis using Mendelian randomization (MR) in East Asian and European populations, respectively. The data we utilized were obtained from the genome-wide association studies (GWAS) database. Various MR methods, including inverse variance weighted (IVW), MR Egger, weighted median, simple median and simple mode were employed to estimate the association between HBV infection and osteoporosis. Heterogeneity analysis and sensitivity tests were performed to ensure the robustness of the results. Bayesian co-localization (coloc) analysis was also applied to calculate the posterior probability of causal variants and to identify common genetic variants between HBV infection and osteoporosis.ResultsMR analysis indicated that HBV infection increased the risk of osteoporosis onset in two East Asian cohort (IVW, OR = 1.058, 95% CI = 1.021 to 1.097, P = 0.002 and OR = 1.067, 95% CI = 1.029 to 1.106, P < 0.001). However, a clear effect of genetic susceptibility to HBV on the enhanced risk of osteoporosis was not observed in two European cohort (IVW, OR = 1.000, 95% CI = 0.999 to 1.001, P = 0.171 and OR = 1.003, 95% CI = 0.981 to 1.025, P = 0.780). Additional MR methods and sensitivity analyses further validated the reliability and robustness of our results. Bayesian co-localization analysis revealed co-localization of HBV infection and osteoporosis on STAT4 at rs11889341based on East Asian GWAS data.ConclusionsOur study identified a causal relationship between HBV infection and osteoporosis in East Asian and European populations. These results provided strong evidence that HBV infection augmented the risk of developing osteoporosis in East Asian populations and provided novel therapeutic targets. |
| format | Article |
| id | doaj-art-b1be8f0181744409bcdde66a410f912a |
| institution | Kabale University |
| issn | 1664-2392 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Endocrinology |
| spelling | doaj-art-b1be8f0181744409bcdde66a410f912a2025-01-22T05:19:37ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922025-01-011510.3389/fendo.2024.14193031419303Causal associations between osteoporosis and HBV infection across Asian and European populations: evidence from Mendelian randomization and colocalization analysisZhengnan Li0Jiarui Cao1Ke Li2Yixin Wu3Zhanpeng Luo4Rui Cao5Zhiheng Cheng6Zhendong Tian7Yiyang Han8Yuping Lai9Bangqi Wang10Shen Chen11Department of Sports Medicine, Ganzhou People’s Hospital, Ganzhou, Jiangxi, ChinaQueen Mary School, Medical College, Nanchang University, Nanchang, ChinaQueen Mary School, Medical College, Nanchang University, Nanchang, ChinaQueen Mary School, Medical College, Nanchang University, Nanchang, ChinaQueen Mary School, Medical College, Nanchang University, Nanchang, ChinaQueen Mary School, Medical College, Nanchang University, Nanchang, ChinaQueen Mary School, Medical College, Nanchang University, Nanchang, ChinaQueen Mary School, Medical College, Nanchang University, Nanchang, ChinaQueen Mary School, Medical College, Nanchang University, Nanchang, ChinaThe Huankui Academy, Nanchang University, Nanchang, Jiangxi, ChinaState Key Laboratory of Molecular Oncology and Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaThe Key Laboratory of Geriatrics, Beijing Institute of Geriatrics, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing Hospital/National Center of Gerontology of National Health Commission, Beijing, ChinaIntroductionClinical studies have demonstrated a potential association between chronic hepatitis caused by hepatitis B virus (HBV) infection and osteoporosis. However, the causal relationship between HBV infection and osteoporosis remains to be determined.MethodsWe investigated whether HBV infection is causally associated with osteoporosis using Mendelian randomization (MR) in East Asian and European populations, respectively. The data we utilized were obtained from the genome-wide association studies (GWAS) database. Various MR methods, including inverse variance weighted (IVW), MR Egger, weighted median, simple median and simple mode were employed to estimate the association between HBV infection and osteoporosis. Heterogeneity analysis and sensitivity tests were performed to ensure the robustness of the results. Bayesian co-localization (coloc) analysis was also applied to calculate the posterior probability of causal variants and to identify common genetic variants between HBV infection and osteoporosis.ResultsMR analysis indicated that HBV infection increased the risk of osteoporosis onset in two East Asian cohort (IVW, OR = 1.058, 95% CI = 1.021 to 1.097, P = 0.002 and OR = 1.067, 95% CI = 1.029 to 1.106, P < 0.001). However, a clear effect of genetic susceptibility to HBV on the enhanced risk of osteoporosis was not observed in two European cohort (IVW, OR = 1.000, 95% CI = 0.999 to 1.001, P = 0.171 and OR = 1.003, 95% CI = 0.981 to 1.025, P = 0.780). Additional MR methods and sensitivity analyses further validated the reliability and robustness of our results. Bayesian co-localization analysis revealed co-localization of HBV infection and osteoporosis on STAT4 at rs11889341based on East Asian GWAS data.ConclusionsOur study identified a causal relationship between HBV infection and osteoporosis in East Asian and European populations. These results provided strong evidence that HBV infection augmented the risk of developing osteoporosis in East Asian populations and provided novel therapeutic targets.https://www.frontiersin.org/articles/10.3389/fendo.2024.1419303/fullosteoporosisHBVSTAT4Mendelian randomizationColocalization analysis |
| spellingShingle | Zhengnan Li Jiarui Cao Ke Li Yixin Wu Zhanpeng Luo Rui Cao Zhiheng Cheng Zhendong Tian Yiyang Han Yuping Lai Bangqi Wang Shen Chen Causal associations between osteoporosis and HBV infection across Asian and European populations: evidence from Mendelian randomization and colocalization analysis Frontiers in Endocrinology osteoporosis HBV STAT4 Mendelian randomization Colocalization analysis |
| title | Causal associations between osteoporosis and HBV infection across Asian and European populations: evidence from Mendelian randomization and colocalization analysis |
| title_full | Causal associations between osteoporosis and HBV infection across Asian and European populations: evidence from Mendelian randomization and colocalization analysis |
| title_fullStr | Causal associations between osteoporosis and HBV infection across Asian and European populations: evidence from Mendelian randomization and colocalization analysis |
| title_full_unstemmed | Causal associations between osteoporosis and HBV infection across Asian and European populations: evidence from Mendelian randomization and colocalization analysis |
| title_short | Causal associations between osteoporosis and HBV infection across Asian and European populations: evidence from Mendelian randomization and colocalization analysis |
| title_sort | causal associations between osteoporosis and hbv infection across asian and european populations evidence from mendelian randomization and colocalization analysis |
| topic | osteoporosis HBV STAT4 Mendelian randomization Colocalization analysis |
| url | https://www.frontiersin.org/articles/10.3389/fendo.2024.1419303/full |
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