Genetic Associations Between Smoking-and Glaucoma-Related Traits

UK Biobank Eye and Vision Consortium, and for the International Glaucoma Genetics Consortium, Jessica H. Tran, Kelsey V. Stuart, Victor de Vries, Joëlle E. Vergroesen, Clara C. Cousins, Pirro G. Hysi, Ron Do, Ghislain Rocheleau, Jae H. Kang, Janey L. Wiggs, Stuart Macgregor, Anthony P. Khawaja, David A. Mackey, Caroline C.W. Klaver, Wishal D. Ramdas, Louis R. Pasquale

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Purpose: The purpose of this study was to describe the genetic relationship between smoking and glaucoma. Methods: We used summary-level genetic data for smoking initiation, smoking intensity (cigarettes per day [CPD]), intraocular pressure (IOP), vertical cup-disc ratio, and open-angle glaucoma (OAG) to estimate global genetic correlations (rg) and perform two-sample Mendelian randomization (MR) experiments that explored relations between traits. Finally, we examined associations between smoking genetic risk scores (GRS) and smoking traits with measured IOP and OAG in Rotterdam Study participants. Results: We identified weak inverse rg between smoking-and glaucoma-related traits that were insignificant after Bonferroni correction. However, MR analysis revealed that genetically predicted smoking initiation was associated with lower IOP (−0.18 mm Hg per SD, 95% confidence interval [CI] = −0.30 to −0.06, P = 0.003). Furthermore, genetically predicted smoking intensity was associated with decreased OAG risk (odds ratio [OR] = 0.74 per SD, 95% CI = 0.61 to 0.90, P = 0.002). In the Rotterdam Study, the smoking initiation GRS was associated with lower IOP (−0.09 mm Hg per SD, 95% CI = −0.17 to −0.01, P = 0.04) and lower odds of OAG (OR = 0.84 per SD, 95% CI = 0.73 to 0.98, P = 0.02) in multivariable-adjusted analyses. In contrast, neither smoking history nor CPD was associated with IOP (P ≥ 0.38) or OAG (P ≥ 0.54). Associations between the smoking intensity GRS and glaucoma traits were null (P ≥ 0.13). Conclusions: MR experiments and GRS generated from Rotterdam Study participants support an inverse relationship between smoking and glaucoma. Translational Relevance: Understanding the genetic drivers of the inverse relationship between smoking and glaucoma could yield new insights into glaucoma pathophysiology.

Original languageEnglish
Article number20
JournalTranslational Vision Science and Technology
Issue number2
Publication statusPublished - Feb 2023


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