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

doi:10.1167/iovs.65.3.12

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 publication › Journal article › Academic research › peer-review

3 Citations (Scopus)

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.

Original language	English
Article number	e2793435
Pages (from-to)	1-12
Number of pages	12
Journal	Investigative Ophthalmology and Visual Science
Volume	65
Issue number	3
DOIs	https://doi.org/10.1167/iovs.65.3.12
Publication status	Published - 5 Mar 2024

Keywords

anxiety
depression
genetic overlap
glaucoma
intraocular pressure

ASJC Scopus subject areas

Ophthalmology
Sensory Systems
Cellular and Molecular Neuroscience

More information

10.1167/iovs.65.3.12

http://hdl.handle.net/10397/107443

Cite this

Zhang, X., Liang, Y., Huang, Y., Liu, S., Li, Q., Wang, S., Wu, G., Du, Z., Wang, Y., Wang, J., Hu, Y., Zang, S., Hu, Y., Shang, X., Zhang, X., Zhang, L., Brown, A., Zhu, Z., He, M., & Yu, H. (2024). Evaluation of the Observational Associations and Shared Genetics Between Glaucoma With Depression and Anxiety. Investigative Ophthalmology and Visual Science, 65(3), 1-12. Article e2793435. https://doi.org/10.1167/iovs.65.3.12

@article{bc21e227f0494dffb5b329b8a347dc98,

title = "Evaluation of the Observational Associations and Shared Genetics Between Glaucoma With Depression and Anxiety",

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.",

keywords = "anxiety, depression, genetic overlap, glaucoma, intraocular pressure",

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

note = "Publisher Copyright: {\textcopyright} 2024 The Authors.",

year = "2024",

month = mar,

day = "5",

doi = "10.1167/iovs.65.3.12",

language = "English",

volume = "65",

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journal = "Investigative Ophthalmology and Visual Science",

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Zhang, X, Liang, Y, Huang, Y, Liu, S, Li, Q, Wang, S, Wu, G, Du, Z, Wang, Y, Wang, J, Hu, Y, Zang, S, Hu, Y, Shang, X, Zhang, X, Zhang, L, Brown, A, Zhu, Z, He, M & Yu, H 2024, 'Evaluation of the Observational Associations and Shared Genetics Between Glaucoma With Depression and Anxiety', Investigative Ophthalmology and Visual Science, vol. 65, no. 3, e2793435, pp. 1-12. https://doi.org/10.1167/iovs.65.3.12

TY - JOUR

T1 - Evaluation of the Observational Associations and Shared Genetics Between Glaucoma With Depression and Anxiety

AU - Zhang, Xiayin

AU - Liang, Yingying

AU - Huang, Yu

AU - Liu, Shunming

AU - Li, Qinyi

AU - Wang, Shan

AU - Wu, Guanrong

AU - Du, Zijing

AU - Wang, Yaxin

AU - Wang, Jinghui

AU - Hu, Yunyan

AU - Zang, Siwen

AU - Hu, Yijun

AU - Shang, Xianwen

AU - Zhang, Xueli

AU - Zhang, Lei

AU - Brown, Andrew

AU - Zhu, Zhuoting

AU - He, Mingguang

AU - Yu, Honghua

PY - 2024/3/5

Y1 - 2024/3/5

N2 - 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.

AB - 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.

KW - anxiety

KW - depression

KW - genetic overlap

KW - glaucoma

KW - intraocular pressure

UR - http://www.scopus.com/inward/record.url?scp=85187451517&partnerID=8YFLogxK

U2 - 10.1167/iovs.65.3.12

DO - 10.1167/iovs.65.3.12

M3 - Journal article

C2 - 38466289

AN - SCOPUS:85187451517

SN - 0146-0404

VL - 65

SP - 1

EP - 12

JO - Investigative Ophthalmology and Visual Science

JF - Investigative Ophthalmology and Visual Science

IS - 3

M1 - e2793435

ER -

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

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