June 2023
Volume 64, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2023
Mendelian Randomization analyses identify environmental factors that influence keratoconus risk
Author Affiliations & Notes
  • Pirro G Hysi
    King's College London Faculty of Life Sciences and Medicine, London, London, United Kingdom
  • Alice E Davidson
    Institute of Ophthalmology, University College London, London, London, United Kingdom
  • Petra Liskova
    Univerzita Karlova 1 lekarska fakulta, Praha, Praha, Czechia
  • Paul N Baird
    University of Melbourne, Melbourne, Victoria, Australia
  • Kathryn P Burdon
    University of Tasmania, Hobart, Tasmania, Australia
  • Christopher J Hammond
    King's College London Faculty of Life Sciences and Medicine, London, London, United Kingdom
  • Alison J Hardcastle
    Institute of Ophthalmology, University College London, London, London, United Kingdom
  • Stephen J Tuft
    Institute of Ophthalmology, University College London, London, London, United Kingdom
    Moorfields Eye Hospital NHS Foundation Trust, London, London, United Kingdom
  • Footnotes
    Commercial Relationships   Pirro Hysi None; Alice Davidson None; Petra Liskova None; Paul Baird None; Kathryn Burdon None; Christopher Hammond None; Alison Hardcastle None; Stephen Tuft None
  • Footnotes
    Support  BrightFocus Foundation G2021011S
Investigative Ophthalmology & Visual Science June 2023, Vol.64, 1178. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Pirro G Hysi, Alice E Davidson, Petra Liskova, Paul N Baird, Kathryn P Burdon, Christopher J Hammond, Alison J Hardcastle, Stephen J Tuft; Mendelian Randomization analyses identify environmental factors that influence keratoconus risk. Invest. Ophthalmol. Vis. Sci. 2023;64(8):1178.

      Download citation file:


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

      ×
  • Supplements
Abstract

Purpose : Early identification and treatment of keratoconus can prevent further visual loss or blindness. Although keratoconus is highly genetic, recent whole-genome association studies explain only about 12.5% of the disease variance in the population. The contribution of environmental factors to keratoconus is even less well understood. This work aims to use genomic-based tools to identify environmental exposures that causally affect keratoconus risk in the population.

Methods : We used Mendelian Randomization (MR) models to assess the presence of causal relationships between environmental exposures and keratoconus. We selected instruments from GWAS summary statistics available from public datasets, such as the GWAS Catalog. Among published SNPs significantly associated with the respective phenotypes (exposures), we selected instrumental variables (IVs) that were fully independent (r2<0.1 and distance >1Mbp). Through MR, we compared IVs association with the exposures and keratoconus in individuals of European ancestry. Specifically, we used two-sample MR simple median, inverse-variance weighted and MR-Egger tests to evaluate the strength of the relationship and test for directional horizontal pleiotropy. We considered the results significant when all three models were at least nominally significant, their estimated confidence intervals overlapped, and the MR-Egger intercept test for pleiotropy was not significant (p>0.05)

Results : Among other exposures, we identified that asthma (PIVW=9.11x10-14) and atopic disease (PIVW=7.57x10-09) we significant causes of keratoconus. For example, keratoconus risk was increased in the presence of hay fever or atopic dermatitis history (ORIVW=1.63, 95% CI 1.43-1.86]) and asthma (ORIVW=1.50, 95% CI 1.11-2.04]). In our dataset none of the IVs or other genetic variants reportedly associated with asthma or other atopic traits showed a significant association with keratoconus. Our MR tests also identified specific metabolic changes that significantly affected the risk of keratoconus.

Conclusions : For the first time, our analyses offer statistical evidence supporting the involvement of specific environmental factors in keratoconus. The significant MR tests in absence of any significant overlapping genetic risk between atopic disease and keratoconus, suggests that atopy acts as an external environmental factor that accounts for a significant proportion of keratoconus risk.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.

×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×