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Comment
. 2023 Dec 14:14:1269069.
doi: 10.3389/fimmu.2023.1269069. eCollection 2023.

Primary biliary cirrhosis and osteoporosis: a bidirectional two-sample Mendelian randomization study

Diqian Zhao #  1 , Guobi Li #  2 , Wenzhe Bai  1 , Jiawen Teng  3 , Bing Yan  4 , Cong Han  5
Affiliations
Comment

Primary biliary cirrhosis and osteoporosis: a bidirectional two-sample Mendelian randomization study

Diqian Zhao et al. Front Immunol. .

Abstract

Background: Observational studies have identified a heightened risk of osteoporosis and fractures in patients with primary biliary cholangitis (PBC). However, conclusive evidence establishing a causal relationship between the two, and a clear mechanism explaining this association, remains elusive.

Methods: We conducted a bidirectional two-sample Mendelian randomization (MR) analysis to investigate the causal relationship between PBC and osteoporosis. This analysis utilized five MR methods: inverse-variance weighted (IVW), MR-Egger, weighted median, weighted mode, and simple mode. Sensitivity analyses were performed, employing various models and testing methods, to assess the impact of heterogeneity and pleiotropy on the results and to confirm their robustness.

Results: A causal relationship between PBC and osteoporosis risk was established through IVW analysis (OR: 1.049, 95%CI: 1.017-1.082, P=0.002). Three other MR analyses corroborated these findings. Conversely, osteoporosis was not found to causally affect PBC risk, as evidenced by IVW analysis (OR: 0.941, 95%CI: 0.783-1.129, P=0.511). Across all MR analyses, no heterogeneity or horizontal pleiotropy was detected among the instrumental variables (IVs). Furthermore, the leave-one-out analysis indicated that no single SNP disproportionately influenced the results, affirming the reliability of the bidirectional MR findings.

Conclusion: This study establishes a positive causal relationship between PBC and the risk of osteoporosis, while no definitive causal link was found from osteoporosis to PBC. These findings offer new insights and guidance for managing bone health in PBC patients.

Keywords: Mendelian randomization study; causal relationship; genome-wide association studies; osteoporosis; primary biliary cirrhosis.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
An overview of this Mendelian randomization (MR) study design; IVs, instrumental variables; MR, Mendelian randomization.
Figure 2
Figure 2
Scatter plot of the effect of primary biliary cholangitis on osteoporosis.
Figure 3
Figure 3
Forest plot of the effect of primary biliary cholangitis on osteoporosis.
Figure 4
Figure 4
Leave-one-out plot of the effect of primary biliary cholangitis on osteoporosis.
Figure 5
Figure 5
Funnel plot of the effect of primary biliary cholangitis on osteoporosis.
Figure 6
Figure 6
Scatter plot of the effect of osteoporosis on primary biliary cholangitis.
Figure 7
Figure 7
Forest plot of the effect of osteoporosis on primary biliary cholangitis.
Figure 8
Figure 8
Leave-one-out plot of the effect of osteoporosis on primary biliary cholangitis.
Figure 9
Figure 9
Funnel plot of the effect of osteoporosis on primary biliary cholangitis.
See this image and copyright information in PMC

Comment on

  • An international genome-wide meta-analysis of primary biliary cholangitis: Novel risk loci and candidate drugs.
    Cordell HJ, Fryett JJ, Ueno K, Darlay R, Aiba Y, Hitomi Y, Kawashima M, Nishida N, Khor SS, Gervais O, Kawai Y, Nagasaki M, Tokunaga K, Tang R, Shi Y, Li Z, Juran BD, Atkinson EJ, Gerussi A, Carbone M, Asselta R, Cheung A, de Andrade M, Baras A, Horowitz J, Ferreira MAR, Sun D, Jones DE, Flack S, Spicer A, Mulcahy VL, Byan J, Han Y, Sandford RN, Lazaridis KN, Amos CI, Hirschfield GM, Seldin MF, Invernizzi P, Siminovitch KA, Ma X, Nakamura M, Mells GF; PBC Consortia; Canadian PBC Consortium; Chinese PBC Consortium; Italian PBC Study Group; Japan-PBC-GWAS Consortium; US PBC Consortium; UK-PBC Consortium. Cordell HJ, et al. J Hepatol. 2021 Sep;75(3):572-581. doi: 10.1016/j.jhep.2021.04.055. Epub 2021 May 23. J Hepatol. 2021. PMID: 34033851 Free PMC article.

References

    1. You H, Ma X, Efe C, Wang G, Jeong S-H, Abe K, et al. . APASL clinical practice guidance: the diagnosis and management of patients with primary biliary cholangitis. Hepatol Int (2022) 16:1–23. doi: 10.1007/s12072-021-10276-6 - DOI - PMC - PubMed
    1. Trivella J, John BV, Levy C. Primary biliary cholangitis: Epidemiology, prognosis, and treatment. Hepatol Commun (2023) 7:e0179. doi: 10.1097/HC9.0000000000000179 - DOI - PMC - PubMed
    1. Hirschfield GM, Beuers U, Corpechot C, Invernizzi P, Jones D, Marzioni M, et al. . EASL Clinical Practice Guidelines: The diagnosis and management of patients with primary biliary cholangitis. J Hepatol (2017) 67:145–72. doi: 10.1016/j.jhep.2017.03.022 - DOI - PubMed
    1. Compston JE, McClung MR, Leslie WD. Osteoporosis. Lancet (2019) 393:364–76. doi: 10.1016/S0140-6736(18)32112-3 - DOI - PubMed
    1. Clynes MA, Harvey NC, Curtis EM, Fuggle NR, Dennison EM, Cooper C. The epidemiology of osteoporosis. Br Med Bull (2020) 133(1):105–17 ldaa005. doi: 10.1093/bmb/ldaa005 - DOI - PMC - PubMed

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