Evaluation of the Observational Associations and Shared Genetics Between Glaucoma With Depression and Anxiety

Xiayin Zhang, Yingying Liang, Yu Huang, Shunming Liu, Qinyi Li, Shan Wang, Guanrong Wu, Zijing Du, Yaxin Wang, Jinghui Wang, Yunyan Hu, Siwen Zang, Yijun Hu, Xianwen Shang, Xueli Zhang, Lei Zhang, Andrew Brown, Zhuoting Zhu, Mingguang He, Honghua Yu

Research output: Journal article publicationJournal articleAcademic researchpeer-review


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.
Original languageEnglish
Article numbere2793435
Pages (from-to)1-12
Number of pages12
JournalInvestigative Ophthalmology and Visual Science
Issue number3
Publication statusPublished - 5 Mar 2024


  • anxiety
  • depression
  • genetic overlap
  • glaucoma
  • intraocular pressure

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience


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