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Genetic Associations Between Smoking- and Glaucoma-Related Traits

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 (OA...

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Autores principales: Tran, Jessica H., Stuart, Kelsey V., de Vries, Victor, Vergroesen, Joëlle E., Cousins, Clara C., Hysi, Pirro G., Do, Ron, Rocheleau, Ghislain, Kang, Jae H., Wiggs, Janey L., MacGregor, Stuart, Khawaja, Anthony P., Mackey, David A., Klaver, Caroline C. W., Ramdas, Wishal D., Pasquale, Louis R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Association for Research in Vision and Ophthalmology 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9932549/
https://www.ncbi.nlm.nih.gov/pubmed/36786746
http://dx.doi.org/10.1167/tvst.12.2.20
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author Tran, Jessica H.
Stuart, Kelsey V.
de Vries, Victor
Vergroesen, Joëlle E.
Cousins, Clara C.
Hysi, Pirro G.
Do, Ron
Rocheleau, Ghislain
Kang, Jae H.
Wiggs, Janey L.
MacGregor, Stuart
Khawaja, Anthony P.
Mackey, David A.
Klaver, Caroline C. W.
Ramdas, Wishal D.
Pasquale, Louis R.
author_facet Tran, Jessica H.
Stuart, Kelsey V.
de Vries, Victor
Vergroesen, Joëlle E.
Cousins, Clara C.
Hysi, Pirro G.
Do, Ron
Rocheleau, Ghislain
Kang, Jae H.
Wiggs, Janey L.
MacGregor, Stuart
Khawaja, Anthony P.
Mackey, David A.
Klaver, Caroline C. W.
Ramdas, Wishal D.
Pasquale, Louis R.
author_sort Tran, Jessica H.
collection PubMed
description 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 (r(g)) 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 r(g) 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.
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spelling pubmed-99325492023-02-17 Genetic Associations Between Smoking- and Glaucoma-Related Traits Tran, Jessica H. Stuart, Kelsey V. de Vries, Victor Vergroesen, Joëlle E. Cousins, Clara C. Hysi, Pirro G. Do, Ron Rocheleau, Ghislain Kang, Jae H. Wiggs, Janey L. MacGregor, Stuart Khawaja, Anthony P. Mackey, David A. Klaver, Caroline C. W. Ramdas, Wishal D. Pasquale, Louis R. Transl Vis Sci Technol Glaucoma 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 (r(g)) 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 r(g) 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. The Association for Research in Vision and Ophthalmology 2023-02-14 /pmc/articles/PMC9932549/ /pubmed/36786746 http://dx.doi.org/10.1167/tvst.12.2.20 Text en Copyright 2023 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
spellingShingle Glaucoma
Tran, Jessica H.
Stuart, Kelsey V.
de Vries, Victor
Vergroesen, Joëlle E.
Cousins, Clara C.
Hysi, Pirro G.
Do, Ron
Rocheleau, Ghislain
Kang, Jae H.
Wiggs, Janey L.
MacGregor, Stuart
Khawaja, Anthony P.
Mackey, David A.
Klaver, Caroline C. W.
Ramdas, Wishal D.
Pasquale, Louis R.
Genetic Associations Between Smoking- and Glaucoma-Related Traits
title Genetic Associations Between Smoking- and Glaucoma-Related Traits
title_full Genetic Associations Between Smoking- and Glaucoma-Related Traits
title_fullStr Genetic Associations Between Smoking- and Glaucoma-Related Traits
title_full_unstemmed Genetic Associations Between Smoking- and Glaucoma-Related Traits
title_short Genetic Associations Between Smoking- and Glaucoma-Related Traits
title_sort genetic associations between smoking- and glaucoma-related traits
topic Glaucoma
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9932549/
https://www.ncbi.nlm.nih.gov/pubmed/36786746
http://dx.doi.org/10.1167/tvst.12.2.20
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