June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
Identification of a Novel Variant Associated with anti-VEGF Response in Age-related Macular Degeneration Using Exome Chip Analysis
Author Affiliations & Notes
  • Michelle Grunin
    Ophthalmology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel
  • Laura Lorés-Motta
    Ophthalmology, Donders Institute for Brain, Cognition and Behaviour, Radboud university medical centre, Nijmegen, Netherlands
  • Moeen Riaz
    Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, East Melbourne, Victoria, Australia
    Ophthalmology, Department of Surgery, University of Melbourne, Melbourne, Victoria, Australia
  • Jordi Corominas
    Human Genetics, Radboud university medical centre, Nijmegen, Netherlands
  • Andrea J. Richardson
    Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, East Melbourne, Victoria, Australia
    Ophthalmology, Department of Surgery, University of Melbourne, Melbourne, Victoria, Australia
  • Sascha Fauser
    Ophthalmology, University Hospital of Cologne, Cologne, Germany
  • Robyn H Guymer
    Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, East Melbourne, Victoria, Australia
    Ophthalmology, Department of Surgery, University of Melbourne, Melbourne, Victoria, Australia
  • Eiko de Jong
    Ophthalmology, Donders Institute for Brain, Cognition and Behaviour, Radboud university medical centre, Nijmegen, Netherlands
  • Iris M Heid
    Genetic Epidemiology, University of Regensburg, Regensburg, Germany
  • Carel C B Hoyng
    Ophthalmology, Donders Institute for Brain, Cognition and Behaviour, Radboud university medical centre, Nijmegen, Netherlands
  • Andrew J Lotery
    Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, United Kingdom
  • Paul Mitchell
    Centre for Vision Research, Department of Ophthalmology and Westmead Millennium Institute for Medical Research, University of Sydney, Sydney, New South Wales, Australia
  • Paul N Baird
    Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, East Melbourne, Victoria, Australia
    Ophthalmology, Department of Surgery, University of Melbourne, Melbourne, Victoria, Australia
  • Anneke I Den Hollander
    Ophthalmology, Donders Institute for Brain, Cognition and Behaviour, Radboud university medical centre, Nijmegen, Netherlands
    Human Genetics, Radboud university medical centre, Nijmegen, Netherlands
  • Itay Chowers
    Ophthalmology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel
  • Footnotes
    Commercial Relationships   Michelle Grunin, None; Laura Lorés-Motta, None; Moeen Riaz, None; Jordi Corominas, None; Andrea Richardson, None; Sascha Fauser, None; Robyn Guymer, None; Eiko de Jong, None; Iris Heid, None; Carel Hoyng, None; Andrew Lotery, None; Paul Mitchell, None; Paul Baird, None; Anneke Den Hollander, None; Itay Chowers, None
  • Footnotes
    Support  Israel Science Foundation
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 1840. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Michelle Grunin, Laura Lorés-Motta, Moeen Riaz, Jordi Corominas, Andrea J. Richardson, Sascha Fauser, Robyn H Guymer, Eiko de Jong, Iris M Heid, Carel C B Hoyng, Andrew J Lotery, Paul Mitchell, Paul N Baird, Anneke I Den Hollander, Itay Chowers; Identification of a Novel Variant Associated with anti-VEGF Response in Age-related Macular Degeneration Using Exome Chip Analysis. Invest. Ophthalmol. Vis. Sci. 2017;58(8):1840.

      Download citation file:


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

      ×
  • Supplements
Abstract

Purpose : The current treatment for neovascular age-related macular degeneration (nvAMD) is by intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) agents, however, a variable treatment outcome has been reported. We aimed to investigate pharmacogenetic associations that may underlie such a differential response.

Methods : The discovery cohort consisted of 678 anti-VEGF treated nvAMD patients (>50 years of age) from 5 different clinics. Patients were identified through the International AMD Genomics Consortium (IAMDGC) and genotyped with a custom exome chip. The main outcome measure was change in visual acuity at 3 months of anti-VEGF treatment (deltaVA). After imputation and quality control, variants with a minor allele frequency ≥0.05 were selected for the analysis. In each cohort, a linear model was performed, adjusted for the first two ancestry principle components, baseline VA and age using EPACTS software, and followed by a meta-analysis on METAL software. Among the top associated variants (p-value <10-5) 6 independant variants were genotyped in 844 patients from five independent cohorts using either KASp or iplex genotyping platform. Finally, a meta-analysis of the top six variants was performed on 1522 patients from 10 cohorts (discovery and replication).

Results : A total of 6,089,769 variants were included in the analysis, and six loci showed a suggestive association with deltaVA at the 3 month time point in all five discovery cohorts (p<1x10-5). After replication of the selected variants, and subsequent meta-analysis of the 10 cohorts (discovery+replication), the top signal which showed consistent association with visual outcome was identified in a locus in and near a chaperonin gene on chromosome 1 (p-value=1.8x10-6, effect= -0.0454±0.0095).

Conclusions : For the first time, we performed a multi-center, large cohort pharmacogenetic GWAS on anti-VEGF treated nvAMD patients. A locus including a chaperonin gene was associated with change in VA following anti-VEGF treatment in nvAMD patients. The results of this study may be potentially used in prediction models for treatment response in nvAMD, and to stratify patients for the best therapeutic option.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.

×
×

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.

×