Objectives

There is still controversy regarding the causal relationship between ankylosing spondylitis (AS) and secondary systemic amyloidosis (SSA). This study utilized aggregated data from genome-wide association studies (GWAS) on population cohorts to investigate whether a causal relationship exists between AS and SSA.

Methods

The genetic causal relationship between AS status and SSA was analyzed utilizing a two-sample Mendelian randomization (TSMR). The analyses were conducted using the weighted mode method (WM²), inverse variance weighted method (IVW), simple mode (SM), weighted median method (WM¹), and Mendelian randomization Egger regression (MR-Egger). Among these methods, the primary results were based on the IVW approach. The association was evaluated using the odds ratio (OR) along with a 95% confidence interval (95% CI).

Results

The IVW analysis revealed a positive causal relationship between AS status and SSA (OR = 1.411, 95 % CI = 1.069, 1.862, P = 0.015). Meanwhile, the WM¹ (OR = 1.394, 95 % CI = 1.115, 1.742, P = 0.004) and WM² (OR = 1.393, 95 % CI = 1.112, 1.743, P = 0.045) methods also identified a positive causal relationship between AS status and SSA. The MR-Egger method did not identify a causal relationship between AS and SSA (OR = 1.175, 95 % CI = 0.888, 1.555, P = 0.342). The SM results demonstrated that the observed genotypes did not exhibit statistically significant differences between AS and SSA (OR = 1.184, 95 % CI = 0.416, 3.366, P = 0.767). The results of the MR-Egger regression suggested that the results were unaffected by bias caused by genetic pleiotropy (Intercept = 0.283, SE = 0.134, P = 0.126). Cochran's Q test did not reveal any significant heterogeneity (Q = 1.759, P = 0.624). The “leave-one-out” analysis further confirmed that the absence of any single SNP did not impact the robustness of our results.

Conclusion

This study revealed a positive causal relationship between AS status and the occurrence of SSA, providing new insights into the genetic analysis of SSA.

中文翻译：

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强直性脊柱炎的状况和继发性系统性淀粉样变性的风险：双样本孟德尔随机研究

目标

关于强直性脊柱炎（AS）与继发性系统性淀粉样变性（SSA）之间的因果关系仍存在争议。本研究利用人群队列全基因组关联研究 (GWAS) 的汇总数据来调查 AS 和 SSA 之间是否存在因果关系。

方法

利用两样本孟德尔随机化 (TSMR) 分析 AS 状态和 SSA 之间的遗传因果关系。^{使用加权众数法(WM 2} )、逆方差加权法(IVW)、简单众数法(SM)、加权中值法(WM ¹ )和孟德尔随机Egger回归(MR-Egger)进行分析。在这些方法中，主要结果基于 IVW 方法。使用比值比 (OR) 和 95% 置信区间 (95% CI) 评估关联性。

结果

IVW 分析显示 AS 状态与 SSA 之间存在正因果关系（OR = 1.411，95% CI = 1.069、1.862，P  = 0.015）。同时，WM ¹（OR = 1.394，95 % CI = 1.115，1.742，P  = 0.004）和WM ²（OR = 1.393，95 % CI = 1.112，1.743，P  = 0.045）方法也确定了两者之间的正因果关系。 AS 状态和 SSA。MR-Egger 方法未发现 AS 和 SSA 之间的因果关系（OR = 1.175，95 % CI = 0.888、1.555，P  = 0.342）。SM 结果表明，观察到的基因型在 AS 和 SSA 之间没有表现出统计学上的显着差异（OR = 1.184，95% CI = 0.416、3.366，P  = 0.767）。MR-Egger回归结果表明，结果不受遗传多效性引起的偏差的影响（Intercept = 0.283，SE = 0.134，P  = 0.126）。Cochran 的 Q 检验未显示任何显着的异质性（Q = 1.759，P  = 0.624）。“留一法”分析进一步证实，任何单一 SNP 的缺失不会影响我们结果的稳健性。

结论

这项研究揭示了 AS 状态与 SSA 发生之间的正因果关系，为 SSA 的遗传分析提供了新的见解。