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Recent studies based on diffusion tensor tractography have suggested an association between glaucoma and brain structural connectivity but have not clarified causality. Methods: To explore the causal associations between glaucoma and brain structural connectivity, a bidirectional Mendelian randomization (MR) study was conducted involving glaucoma and 206 diffusion tensor tractography traits. Highly associated genetic variations were applied as instrumental variables and statistical data were sourced from the database of FinnGen and UK Biobank. The inverse-variance weighted method was applied to assess causal relationships. Additional sensitivity analyses were also performed. Results: Glaucoma was potentially causally associated with alterations in three brain structural connectivities (from the SN to the thalamus, from the DAN to the putamen, and within the LN network) in the forward MR analysis, whereas the inverse MR results identified thirteen brain structural connectivity traits with a potential causal relationship to the risk of glaucoma. Both forward and reverse MR analyses satisfied the sensitivity test with no significant horizontal pleiotropy or heterogeneity. Conclusions: This study offered suggestive evidence for the potential causality between the risk of glaucoma and brain structural connectivity. Our findings also provided novel insights into the neurodegenerative mechanism of glaucoma.<\/jats:p>","DOI":"10.3390\/brainsci14101030","type":"journal-article","created":{"date-parts":[[2024,10,17]],"date-time":"2024-10-17T08:56:32Z","timestamp":1729155392000},"page":"1030","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Association Between Glaucoma and Brain Structural Connectivity Based on Diffusion Tensor Tractography: A Bidirectional Mendelian Randomization Study"],"prefix":"10.3390","volume":"14","author":[{"given":"Lian","family":"Shu","sequence":"first","affiliation":[{"name":"Department of Ophthalmology & Visual Science, Eye & ENT Hospital, Shanghai Medical College, Fudan University, Shanghai 200031, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3206-0070","authenticated-orcid":false,"given":"Xiaoxiao","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology & Visual Science, Eye & ENT Hospital, Shanghai Medical College, Fudan University, Shanghai 200031, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xinghuai","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology & Visual Science, Eye & ENT Hospital, Shanghai Medical College, Fudan University, Shanghai 200031, China"},{"name":"State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan University, Shanghai 200032, China"},{"name":"NHC Key Laboratory of Myopia, Chinese Academy of Medical Sciences, and Shanghai Key Laboratory of Visual Impairment and Restoration (Fudan University), Shanghai 200031, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,10,17]]},"reference":[{"key":"ref_1","first-page":"887","article-title":"Glaucoma Is Second Leading Cause of Blindness Globally","volume":"82","author":"Kingman","year":"2004","journal-title":"Bull. 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