Genetic Associations Between Smoking- and Glaucoma-Related Traits

Jessica H Tran; Kelsey V Stuart; UK Biobank Eye and Vision Consortium, and for the International Glaucoma Genetics Consortium; 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

doi:10.1167/tvst.12.2.20

Genetic Associations Between Smoking- and Glaucoma-Related Traits

Jessica H Tran, Kelsey V Stuart, UK Biobank Eye and Vision Consortium, and for the International Glaucoma Genetics Consortium, 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

Ophthalmology

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Abstract

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 language	English
Article number	20
Pages (from-to)	20
Number of pages	1
Journal	Translational Vision Science & Technology
Volume	12
Issue number	2
DOIs	https://doi.org/10.1167/tvst.12.2.20
Publication status	Published - 1 Feb 2023

Bibliographical note

Acknowledgments
Supported by NEI R01 015473, an unrestricted Challenge Grant from Research to Prevent Blindness (NYC), and the Glaucoma Foundation. The Rotterdam Study is supported by the Erasmus Medical Center and Erasmus University Rotterdam, the Netherlands Organization for Scientific Research (NWO), in particular through NWO Grant 91815655, the Netherlands Organization for Health Research and Development (ZonMw), the Research Institute for Diseases in the Elderly (RIDE); the Ministry of Education, Culture and Science, the Ministry of Health, Welfare and Sports, the European Commission (DG XII), the European Research Council (ERC) under the European Union's Horizon 2020 Research and Innovation Programme Grant 648268, and the Municipality of Rotterdam. Additional support was given by Stichting Glaucoomfonds, Landelijke Stichting voor Blinden en Slechtzienden (LSBS), Stichting Oogfonds Nederland, Rotterdamse Stichting Blindenbelangen (RSB), Stichting Lijf en Leven, Henkes Stichting, Stichting voor Ooglijders, and Stichting Blindenhulp. The sponsor or funding organizations had no role in the design or conduct of this research.

Copyright 2023 The Authors

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Tran, J. H., Stuart, K. V., UK Biobank Eye and Vision Consortium, and for the International Glaucoma Genetics Consortium, de Vries, V., Vergroesen, J. E., Cousins, C. C., Hysi, P. G., Do, R., Rocheleau, G., Kang, J. H., Wiggs, J. L., MacGregor, S., Khawaja, A. P., Mackey, D. A., Klaver, C. C. W., Ramdas, W. D., & Pasquale, L. R. (2023). Genetic Associations Between Smoking- and Glaucoma-Related Traits. Translational Vision Science & Technology, 12(2), 20. [20]. https://doi.org/10.1167/tvst.12.2.20

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abstract = "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.",

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

note = "Acknowledgments Supported by NEI R01 015473, an unrestricted Challenge Grant from Research to Prevent Blindness (NYC), and the Glaucoma Foundation. The Rotterdam Study is supported by the Erasmus Medical Center and Erasmus University Rotterdam, the Netherlands Organization for Scientific Research (NWO), in particular through NWO Grant 91815655, the Netherlands Organization for Health Research and Development (ZonMw), the Research Institute for Diseases in the Elderly (RIDE); the Ministry of Education, Culture and Science, the Ministry of Health, Welfare and Sports, the European Commission (DG XII), the European Research Council (ERC) under the European Union's Horizon 2020 Research and Innovation Programme Grant 648268, and the Municipality of Rotterdam. Additional support was given by Stichting Glaucoomfonds, Landelijke Stichting voor Blinden en Slechtzienden (LSBS), Stichting Oogfonds Nederland, Rotterdamse Stichting Blindenbelangen (RSB), Stichting Lijf en Leven, Henkes Stichting, Stichting voor Ooglijders, and Stichting Blindenhulp. The sponsor or funding organizations had no role in the design or conduct of this research. Copyright 2023 The Authors",

year = "2023",

month = feb,

day = "1",

doi = "10.1167/tvst.12.2.20",

language = "English",

volume = "12",

pages = "20",

journal = "Translational Vision Science and Technology",

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Tran, JH, Stuart, KV, UK Biobank Eye and Vision Consortium, and for the International Glaucoma Genetics Consortium, de Vries, V, Vergroesen, JE, Cousins, CC, Hysi, PG, Do, R, Rocheleau, G, Kang, JH, Wiggs, JL, MacGregor, S, Khawaja, AP, Mackey, DA, Klaver, CCW , Ramdas, WD & Pasquale, LR 2023, 'Genetic Associations Between Smoking- and Glaucoma-Related Traits', Translational Vision Science & Technology, vol. 12, no. 2, 20, pp. 20. https://doi.org/10.1167/tvst.12.2.20

Genetic Associations Between Smoking- and Glaucoma-Related Traits. / Tran, Jessica H; Stuart, Kelsey V; UK Biobank Eye and Vision Consortium, and for the International Glaucoma Genetics Consortium et al.
In: Translational Vision Science & Technology, Vol. 12, No. 2, 20, 01.02.2023, p. 20.

Research output: Contribution to journal › Article › Academic › peer-review

TY - JOUR

T1 - Genetic Associations Between Smoking- and Glaucoma-Related Traits

AU - Tran, Jessica H

AU - Stuart, Kelsey V

AU - UK Biobank Eye and Vision Consortium, and for the International Glaucoma Genetics Consortium

AU - de Vries, Victor

AU - Vergroesen, Joëlle E

AU - Cousins, Clara C

AU - Hysi, Pirro G

AU - Do, Ron

AU - Rocheleau, Ghislain

AU - Kang, Jae H

AU - Wiggs, Janey L

AU - MacGregor, Stuart

AU - Khawaja, Anthony P

AU - Mackey, David A

AU - Klaver, Caroline C W

AU - Ramdas, Wishal D

AU - Pasquale, Louis R

N1 - Acknowledgments Supported by NEI R01 015473, an unrestricted Challenge Grant from Research to Prevent Blindness (NYC), and the Glaucoma Foundation. The Rotterdam Study is supported by the Erasmus Medical Center and Erasmus University Rotterdam, the Netherlands Organization for Scientific Research (NWO), in particular through NWO Grant 91815655, the Netherlands Organization for Health Research and Development (ZonMw), the Research Institute for Diseases in the Elderly (RIDE); the Ministry of Education, Culture and Science, the Ministry of Health, Welfare and Sports, the European Commission (DG XII), the European Research Council (ERC) under the European Union's Horizon 2020 Research and Innovation Programme Grant 648268, and the Municipality of Rotterdam. Additional support was given by Stichting Glaucoomfonds, Landelijke Stichting voor Blinden en Slechtzienden (LSBS), Stichting Oogfonds Nederland, Rotterdamse Stichting Blindenbelangen (RSB), Stichting Lijf en Leven, Henkes Stichting, Stichting voor Ooglijders, and Stichting Blindenhulp. The sponsor or funding organizations had no role in the design or conduct of this research. Copyright 2023 The Authors

PY - 2023/2/1

Y1 - 2023/2/1

N2 - 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.

AB - 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.

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U2 - 10.1167/tvst.12.2.20

DO - 10.1167/tvst.12.2.20

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C2 - 36786746

SN - 2164-2591

VL - 12

SP - 20

JO - Translational Vision Science and Technology

JF - Translational Vision Science and Technology

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ER -

Genetic Associations Between Smoking- and Glaucoma-Related Traits

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