June 2022
Volume 63, Issue 7
Open Access
ARVO Annual Meeting Abstract  |   June 2022
Genetic correlations between smoking- and glaucoma-related traits
Author Affiliations & Notes
  • Jessica H. Tran
    Ophthalmology, Icahn School of Medicine at Mount Sinai, New York, New York, United States
  • Kelsey V. Stuart
    NIHR Biomedical Research Centre, Moorfields Eye Hospital NHS Foundation Trust, London, London, United Kingdom
  • Clara Cousins
    Massachusetts Eye and Ear Department of Ophthalmology, Boston, Massachusetts, United States
  • Pirro G Hysi
    Ophthalmology, King's College London, London, London, United Kingdom
    Twin Research & Genetic Epidemiology, King's College London, London, London, United Kingdom
  • Anthony P Khawaja
    NIHR Biomedical Research Centre, Moorfields Eye Hospital NHS Foundation Trust, London, London, United Kingdom
  • Ron Do
    Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai Department of Genetics and Genomic Sciences, New York, New York, United States
  • Shantanu Bafna
    Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai Department of Genetics and Genomic Sciences, New York, New York, United States
  • Jae Kang
    Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, Massachusetts, United States
  • Jiali Wang
    Massachusetts Eye and Ear Department of Ophthalmology, Boston, Massachusetts, United States
  • Stuart MacGregor
    Statistical Genetics, QIMR Berghofer Medical Research Institute, Queensland, Australia
  • Janey L Wiggs
    Massachusetts Eye and Ear Department of Ophthalmology, Boston, Massachusetts, United States
  • Louis R Pasquale
    Ophthalmology, Icahn School of Medicine at Mount Sinai, New York, New York, United States
  • Footnotes
    Commercial Relationships   Jessica Tran None; Kelsey Stuart None; Clara Cousins None; Pirro Hysi None; Anthony Khawaja None; Ron Do None; Shantanu Bafna None; Jae Kang None; Jiali Wang None; Stuart MacGregor None; Janey Wiggs None; Louis Pasquale Skye Bioscience, Code C (Consultant/Contractor)
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science June 2022, Vol.63, 1133. doi:
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    • Get Citation

      Jessica H. Tran, Kelsey V. Stuart, Clara Cousins, Pirro G Hysi, Anthony P Khawaja, Ron Do, Shantanu Bafna, Jae Kang, Jiali Wang, Stuart MacGregor, Janey L Wiggs, Louis R Pasquale; Genetic correlations between smoking- and glaucoma-related traits. Invest. Ophthalmol. Vis. Sci. 2022;63(7):1133.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : We assessed global cross-trait genetic correlations between glaucoma- and smoking-related traits to gain insights into the pathogenesis of primary open-angle glaucoma (POAG).

Methods : We gathered publicly available genome-wide association study summary statistics from participants of European-ancestry regarding the following glaucoma-related traits: intraocular pressure (IOP; n=139,555), macula retinal nerve fiber layer (mRNFL; n=31,434) thickness, macula ganglion cell-inner plexiform layer (mGCIPL; n=31,434) thickness, vertical cup-disc ratio (vCDR; n=23,899), artificial intelligence-determined vertical cup-disc ratio (AI-vCDR; n=111,724) and POAG (n=216,257). We gathered similar data for the following smoking-related traits: smoking initiation (n=1,232,971; defined as ever having been a regular smoker) and cigarettes smoked per day (CPD; n=337,334). We estimated genetic correlations (rg) between traits using linkage disequilibrium score regression and tested for causal associations using two-sample Mendelian randomization (MR). The threshold of significance was Bonferroni-corrected for multiple comparisons.

Results : There were positive global genetic correlations between POAG and IOP (rg=0.68; p<1E-100), vCDR (rg=0.51; p=4.15E-20) and AI-vCDR (rg=0.56; p=3.57E-50). There was no global genetic correlation between POAG and mRNFL (rg=-0.082; p=0.07) or mGCIPL (rg=-0.03; p=0.55). There were also global genetic correlations between IOP and AI-vCDR (rg=0.28; p=1.29E-31) and vCDR (rg =0.19; p=2.16E-6). There were nominal non-significant inverse global genetic correlations between smoking initiation and POAG (rg =-0.05, p=0.05), IOP (rg =-0.06, p=0.01), mGCIPL (rg = -0.07, p=0.03) and AI-vCDR (rg =-0.04, p=0.03). CPD and IOP also exhibited nominal inverse correlations (rg=-0.06, p=0.04). Inverse variance weighted MR analyses revealed a significant association between smoking initiation and IOP (-0.18mmHg per standard deviation increase in the smoking initiation instrument, 95% confidence interval: -0.30 to -0.06, p=3.0E-4). A similar significant association was observed with MR-PRESSO, but not with other MR methods.

Conclusions : While shared genetic correlation between smoking- and glaucoma-related traits were nominal, MR analyses demonstrate a possible causal link between smoking initiation and IOP. Further efforts could define shared loci between IOP and smoking initiation that might lead to new drug targets for glaucoma.

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.

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