Zhang Jun, Hu Shuqiong, Luo Xiang, Huang Changwei, Cao Qingfeng
Chongqing Key Laboratory of Ophthalmology, and Chongqing Eye Institute, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People's Republic of China.
Wuhan Aier Eye Hospital of Wuhan University, Wuhan, Hubei Province, People's Republic of China.
Int Ophthalmol. 2023 Feb;43(2):589-596. doi: 10.1007/s10792-022-02462-8. Epub 2022 Aug 10.
The objective of this article was to examine the potential effect of juvenile idiopathic arthritis-associated uveitis (JIAU) on the risk of major depressive and anxiety disorders through Mendelian randomization (MR) study.
Genetic instrumental variables from the largest available genome-wide association study for JIAU, major depressive disorder, and anxiety disorder were applied. A set of complementary MR approaches including inverse-variance weighted (IVW) were carried out to verify the estimate association and assess horizontal pleiotropy.
Our results indicated that genetically driven JIAU did not causally produce changes in major depressive or anxiety disorders (IVW: OR = 1.001, 95% CI = 0.997-1.006, P = 0.581; IVW: OR = 1.006, 95% CI = 0.980-1.033, P = 0.649, respectively). In addition, the risk of JIAU could not be influenced by genetically predicted major depressive or anxiety disorders (IVW: OR = 1.132, 95% CI = 0.914-1.404, P = 0.256; IVW: OR = 1.019, 95% CI = 0.548-1.896, P = 0.953, respectively). Besides, several sensitivity analyses indicated that our MR results were robust and no horizontal pleiotropy was observed (P > 0.05).
Our MR study does not reveal sufficient evidence to support the causal association of JIAU with the development of major depressive or anxiety disorders in both directions. Further large studies are warranted to validate the undetermined relationship between JIAU and the risk of major depressive or anxiety disorders.
本文旨在通过孟德尔随机化（MR）研究，探讨青少年特发性关节炎相关性葡萄膜炎（JIAU）对重度抑郁和焦虑症风险的潜在影响。
应用来自现有最大规模的全基因组关联研究中关于JIAU、重度抑郁症和焦虑症的遗传工具变量。采用一组包括逆方差加权（IVW）在内的互补MR方法来验证估计的关联性并评估水平多效性。
我们的结果表明，遗传驱动的JIAU不会因果性地导致重度抑郁或焦虑症的变化（IVW：比值比[OR]=1.001，95%置信区间[CI]=0.997 - 1.006，P = 0.581；IVW：OR = 1.006，95% CI = 0.980 - 1.033，P = 0.649）。此外，JIAU的风险不受遗传预测的重度抑郁或焦虑症的影响（IVW：OR = 1.132，95% CI = 0.914 - 1.404，P = 0.256；IVW：OR = 1.019，95% CI = 0.548 - 1.896，P = 0.953）。此外，多项敏感性分析表明我们的MR结果具有稳健性，未观察到水平多效性（P > 0.05）。
我们的MR研究没有揭示足够的证据来支持JIAU与重度抑郁或焦虑症发生在两个方向上的因果关联。需要进一步的大型研究来验证JIAU与重度抑郁或焦虑症风险之间尚未确定的关系。
