Evaluation of the Observational Associations and Shared Genetics Between Glaucoma With Depression and Anxiety.
Zhang Xiayin, Liang Yingying, Huang Yu, Liu Shunming, Li Qinyi, Wang Shan, Wu Guanrong, Du Zijing, Wang Yaxin, Wang Jinghui
AI Summary
This study found glaucoma is linked to higher depression/anxiety risk, driven by shared genetic factors, not direct causation. Clinically, this highlights the need for holistic patient care.
Abstract
Purpose
Glaucoma, a leading cause of blindness worldwide, is suspected to exhibit a notable association with psychological disturbances. This study aimed to investigate epidemiological associations and explore shared genetic architecture between glaucoma and mental traits, including depression and anxiety.
Methods
Multivariable logistic regression and Cox proportional hazards regression models were employed to investigate longitudinal associations based on UK Biobank. A stepwise approach was used to explore the shared genetic architecture. First, linkage disequilibrium score regression inferred global genetic correlations. Second, MiXeR analysis quantified the number of shared causal variants. Third, specific shared loci were detected through conditional/conjunctional false discovery rate (condFDR/conjFDR) analysis and characterized for biological insights. Finally, two-sample Mendelian randomization (MR) was conducted to investigate bidirectional causal associations.
Results
Glaucoma was significantly associated with elevated risks of hospitalized depression (hazard ratio [HR] = 1.54; 95% confidence interval [CI], 1.01-2.34) and anxiety (HR = 2.61; 95% CI, 1.70-4.01) compared to healthy controls. Despite the absence of global genetic correlations, MiXeR analysis revealed 300 variants shared between glaucoma and depression, and 500 variants shared between glaucoma and anxiety. Subsequent condFDR/conjFDR analysis discovered 906 single-nucleotide polymorphisms (SNPs) jointly associated with glaucoma and depression and two associated with glaucoma and anxiety. The MR analysis did not support robust causal associations but indicated the existence of pleiotropic genetic variants influencing both glaucoma and depression.
Conclusions
Our study enhances the existing epidemiological evidence and underscores the polygenic overlap between glaucoma and mental traits. This observation suggests a correlation shaped by pleiotropic genetic variants rather than being indicative of direct causal relationships.
MeSH Terms
Shields Classification
Key Concepts6
Glaucoma was significantly associated with elevated risks of hospitalized depression (hazard ratio [HR] = 1.54; 95% confidence interval [CI], 1.01-2.34) compared to healthy controls.
Glaucoma was significantly associated with elevated risks of hospitalized anxiety (HR = 2.61; 95% CI, 1.70-4.01) compared to healthy controls.
MiXeR analysis revealed 300 genetic variants shared between glaucoma and depression.
MiXeR analysis revealed 500 genetic variants shared between glaucoma and anxiety.
Conditional/conjunctional false discovery rate (condFDR/conjFDR) analysis discovered 906 single-nucleotide polymorphisms (SNPs) jointly associated with glaucoma and depression.
Two-sample Mendelian randomization (MR) analysis did not support robust causal associations between glaucoma and depression or anxiety but indicated the existence of pleiotropic genetic variants influencing both glaucoma and depression.
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