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ORIGINAL RESEARCH article

Front. Endocrinol.
Sec. Bone Research
Volume 15 - 2024 | doi: 10.3389/fendo.2024.1419303
This article is part of the Research Topic Organ System Crosstalk in Degenerative Musculoskeletal Diseases View all 11 articles

Causal Associations Between Osteoporosis and HBV Infection Across Asian and European Populations: Evidence from Mendelian Randomization and Colocalization Analysis

Provisionally accepted
Zhengnan Li Zhengnan Li 1*Jiarui Cao Jiarui Cao 2Ke Li Ke Li 2*Yixin Wu Yixin Wu 2*Zhanpeng Luo Zhanpeng Luo 2Rui Cao Rui Cao 2*Zhiheng Cheng Zhiheng Cheng 2*Zhendong Tian Zhendong Tian 2*Yiyang Han Yiyang Han 2*Yuping Lai Yuping Lai 3*Bangqi Wang Bangqi Wang 4*Shen Chen Shen Chen 5*
  • 1 Department of Sports Medicine, Ganzhou People's Hospital, Ganzhou, Jiangxi, China
  • 2 Queen Mary school, Medical College, Nanchang University, Nanchang, China
  • 3 Huankui Academy, Nanchang University, Nanchang, Jiangxi Province, China
  • 4 National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
  • 5 The Key Laboratory of Geriatrics, Beijing Hospital, Chinese Academy of Medical Sciences, Beijing, China

The final, formatted version of the article will be published soon.

    Clinical 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.We 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.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 colocalization analysis revealed co-localization of HBV infection and osteoporosis on STAT4 at rs11889341 based on East Asian GWAS data.Our 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.

    Keywords: Osteoporosis, HBV, STAT4, Mendelian randomization, Colocalization analysis

    Received: 18 Apr 2024; Accepted: 19 Dec 2024.

    Copyright: © 2024 Li, Cao, Li, Wu, Luo, Cao, Cheng, Tian, Han, Lai, Wang and Chen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Zhengnan Li, Department of Sports Medicine, Ganzhou People's Hospital, Ganzhou, Jiangxi, China
    Ke Li, Queen Mary school, Medical College, Nanchang University, Nanchang, China
    Yixin Wu, Queen Mary school, Medical College, Nanchang University, Nanchang, China
    Rui Cao, Queen Mary school, Medical College, Nanchang University, Nanchang, China
    Zhiheng Cheng, Queen Mary school, Medical College, Nanchang University, Nanchang, China
    Zhendong Tian, Queen Mary school, Medical College, Nanchang University, Nanchang, China
    Yiyang Han, Queen Mary school, Medical College, Nanchang University, Nanchang, China
    Yuping Lai, Huankui Academy, Nanchang University, Nanchang, 330031, Jiangxi Province, China
    Bangqi Wang, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
    Shen Chen, The Key Laboratory of Geriatrics, Beijing Hospital, Chinese Academy of Medical Sciences, Beijing, China

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