Pan Lingai, Zhou Guangpeng, Wei Guocui, Zhao Qian, Wang Yanping, Chen Qianlan, Xiao Qing, Song Yujie, Liang Xiangui, Zou Zhili, Li Xiuxia, Xiong Xuan
Department of Intensive Care Unit, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.
Endocrine Department, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.
Front Psychiatry. 2024 Oct 16;15:1465381. doi: 10.3389/fpsyt.2024.1465381. eCollection 2024.
Psychiatric disorders, such as major depressive disorder (MDD), anxiety disorder (AD), bipolar disorder (BD), and schizophrenia (SCZ), are disturbances in brain activity that lead to disorders of cognition, behavior, and emotion regulation. Among Sjogren syndrome (SS) patients, psychiatric disorders are more prevalent than in the general population. Identifying associated risk factors can provide new evidence for clinical diagnosis and treatment.
We selected genetic instruments based on published genome-wide association studies (GWASs) to determine predisposition. Then, we conducted a 2-sample bidirectional Mendelian randomization (MR) analysis to explore the potential causal associations between SS and four major psychiatric disorders. The primary analysis was performed using MR with the inverse-variance weighted method. Confirmation was achieved through Steiger filtering and testing to determine the causal direction. Sensitivity analyses were conducted using MR-Egger, MR-PRESSO, and "leave-one-out" method methods.
Our study showed that SS was linked to BD and SCZ, indicating that individuals with SS may have a reduced risk of developing BD (IVW: OR = 0.940, =0.014) and SCZ (IVW: OR = 0.854, =1.47*10-4), while there was no causal relationship between SS and MDD or AD. MR-Egger regression shows no evidence of pleiotropy (BD: intercept = 0.007, p = 0.774; SCZ: intercept = 0.051, p = 0.209). The same as the MR-PRESSO analysis (BD: global test p = 1.000; SCZ: global test p = 0.160). However, the results from the leave-one-out analysis demonstrated instability. Specifically, after excluding SNP rs3117581, the effects on BD and SCZ were found to be non-significant, suggesting the potential influence of unrecognized confounding factors. The results of the reverse MR show that four major psychiatric disorders had no causal effects on SS.
Our research findings demonstrate a causal relationship between SS and SCZ, as well as between SS and BD. There are no causal effects between the four major psychiatric disorders and SS. These findings suggest that SS may have the potential to reduce the risk of both psychiatric disorders. This study provides new insight for their prevention and treatment.
精神疾病，如重度抑郁症（MDD）、焦虑症（AD）、双相情感障碍（BD）和精神分裂症（SCZ），是大脑活动的紊乱，会导致认知、行为和情绪调节障碍。在干燥综合征（SS）患者中，精神疾病比普通人群更为普遍。识别相关危险因素可为临床诊断和治疗提供新证据。
我们根据已发表的全基因组关联研究（GWAS）选择遗传工具来确定易感性。然后，我们进行了两样本双向孟德尔随机化（MR）分析，以探索SS与四种主要精神疾病之间的潜在因果关联。主要分析采用逆方差加权法进行MR分析。通过Steiger过滤和检验来确定因果方向以进行确认。使用MR-Egger、MR-PRESSO和“留一法”进行敏感性分析。
我们的研究表明，SS与BD和SCZ相关，这表明SS患者患BD（IVW：OR = 0.940， =0.014）和SCZ（IVW：OR = 0.854， =1.47×10-4）的风险可能降低，而SS与MDD或AD之间没有因果关系。MR-Egger回归显示没有多效性证据（BD：截距 = 0.007，p = 0.774；SCZ：截距 = 0.051，p = 0.209）。与MR-PRESSO分析相同（BD：全局检验p = 1.000；SCZ：全局检验p = 0.160）。然而，留一法分析的结果显示不稳定。具体而言，排除SNP rs3117581后，发现对BD和SCZ的影响不显著，这表明存在未被识别的混杂因素的潜在影响。反向MR的结果表明，四种主要精神疾病对SS没有因果效应。
我们的研究结果表明SS与SCZ之间以及SS与BD之间存在因果关系。四种主要精神疾病与SS之间没有因果效应。这些发现表明，SS可能具有降低这两种精神疾病风险的潜力。本研究为它们的预防和治疗提供了新的见解。
