目的: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。本研究利用来自全基因组关联研究(GWAS)人群队列的汇总数据来调查AS和SSA之间是否存在因果关系。
方法:使用双样本孟德尔随机化(TSMR)分析了AS状态和SSA之间的遗传因果关系。分析使用加权模式方法(WM2)进行,方差逆加权法(IVW),简单模式(SM),加权中位数法(WM1),和孟德尔随机化Egger回归(MR-Egger)。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。
结果:IVW分析显示AS状态与SSA之间存在正的因果关系(OR=1.411,95%CI=1.069,1.862,P=0.015)。同时,WM1(OR=1.394,95%CI=1.115,1.742,P=0.004)和WM2(OR=1.393,95%CI=1.112,1.743,P=0.045)方法也确定了AS状态和SSA之间的正因果关系。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倚影响(截距=0.283,SE=0.134,P=0.126)。Cochran的Q检验没有发现任何显著的异质性(Q=1.759,P=0.624)。“留一法”分析进一步证实,不存在任何单个SNP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的遗传分析提供新的见解。
OBJECTIVE: 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.
CONCLUSIONS: This study revealed a positive causal relationship between AS status and the occurrence of SSA, providing new insights into the genetic analysis of SSA.