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Comment
. 2024 Feb 6:15:1297454.
doi: 10.3389/fimmu.2024.1297454. eCollection 2024.

Causality between Ankylosing Spondylitis and osteoarthritis in European ancestry: a bidirectional Mendelian randomization study

Yangguang Lu #  1 , Di Lu #  2 , Hongzhi Zhang  1 , Haoyang Li  1 , Bohuai Yu  1 , Yige Zhang  1 , Hantao Hu  1 , Hongfeng Sheng  2
Affiliations
Comment

Causality between Ankylosing Spondylitis and osteoarthritis in European ancestry: a bidirectional Mendelian randomization study

Yangguang Lu et al. Front Immunol. .

Abstract

Objective: To explore the bidirectional causal relationship between Ankylosing Spondylitis (AS) and Osteoarthritis (OA) at the genetic level within the European ancestry.

Methods: We implemented a series of quality control steps to select instrumental variables (IVs) related to the exposure. We conducted two-sample Mendelian randomization (MR) using the inverse-variance weighted method as the primary approach. We adjusted significance levels using Bonferroni correction, assessed heterogeneity using Cochrane's Q test. Sensitivity analysis was conducted through leave-one-out method. Additionally, external datasets and relaxed IV selection criteria were employed, and multivariate MR analyses were performed for validation purposes. Finally, Bayesian colocalization (COLOC) analysis identified common genes, validating the MR results.

Results: The investigation focused on the correlation between OA and AS in knee, hip, and hand joints. MR results revealed that individuals with AS exhibit a decreased risk of knee OA (OR = 0.9882, 95% CI: 0.9804-0.9962) but no significant increase in the risk of hip OA (OR = 0.9901, 95% CI: 0.9786-1.0018). Conversely, AS emerged as a risk factor for hand OA (OR = 1.0026, 95% CI: 1.0015-1.0036). In reverse-direction MR analysis, OA did not significantly influence the occurrence of AS. Importantly, minimal heterogeneity was observed in our MR analysis results (p > 0.05), and the robustness of these findings was confirmed through sensitivity analysis and multivariate MR analysis. COLOC analysis identified four colocalized variants for AS and hand OA (rs74707996, rs75240935, rs181468789, and rs748670681).

Conclusion: In European population, individuals with AS have a relatively lower risk of knee OA, whereas AS serves as a risk factor for hand OA. However, no significant causal relationship was found between AS and hip OA. Additionally, it offers novel insights into genetic research on AS and OA.

Keywords: Ankylosing Spondylitis; Mendelian randomization; genetic analyses; inflammation; orthopedics; osteoarthritis.

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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
Flowchart of the study design overview.
Figure 2
Figure 2
Forest plots of the results on two-sample bidirectional Mendelian randomization analysis. OR, Odds ratio.
Figure 3
Figure 3
Scatter and funnel plots of the results of Mendelian randomization with AS as an exposure factor. (A) Scatterplot with knee OA as the outcome; (B) Scatterplot with hip OA as the outcome; (C) Scatterplot with hand OA as the outcome; (D) Funnel plot with knee OA as the outcome; (E) Funnel plot with hip OA as the outcome; (F) Funnel plot with hand OA as the outcome.
See this image and copyright information in PMC

Comment on

  • Deciphering osteoarthritis genetics across 826,690 individuals from 9 populations.
    Boer CG, Hatzikotoulas K, Southam L, Stefánsdóttir L, Zhang Y, Coutinho de Almeida R, Wu TT, Zheng J, Hartley A, Teder-Laving M, Skogholt AH, Terao C, Zengini E, Alexiadis G, Barysenka A, Bjornsdottir G, Gabrielsen ME, Gilly A, Ingvarsson T, Johnsen MB, Jonsson H, Kloppenburg M, Luetge A, Lund SH, Mägi R, Mangino M, Nelissen RRGHH, Shivakumar M, Steinberg J, Takuwa H, Thomas LF, Tuerlings M; arcOGEN Consortium; HUNT All-In Pain; ARGO Consortium; Regeneron Genetics Center; Babis GC, Cheung JPY, Kang JH, Kraft P, Lietman SA, Samartzis D, Slagboom PE, Stefansson K, Thorsteinsdottir U, Tobias JH, Uitterlinden AG, Winsvold B, Zwart JA, Davey Smith G, Sham PC, Thorleifsson G, Gaunt TR, Morris AP, Valdes AM, Tsezou A, Cheah KSE, Ikegawa S, Hveem K, Esko T, Wilkinson JM, Meulenbelt I, Lee MTM, van Meurs JBJ, Styrkársdóttir U, Zeggini E. Boer CG, et al. Cell. 2021 Sep 2;184(18):4784-4818.e17. doi: 10.1016/j.cell.2021.07.038. Epub 2021 Aug 26. Cell. 2021. PMID: 34450027 Free PMC article.

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