July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
Genome-wide association study of primary open-angle glaucoma in continental and admixed African populations.
Author Affiliations & Notes
  • Pieter W.M. Bonnemaijer
    Department of Ophthalmology & Epidemiology, Erasmus MC, Rotterdam, Netherlands
    The Rotterdam Eye Hospital, Rotterdam, Netherlands
  • Adriana I Iglesias
    Department of Ophthalmology & Epidemiology, Erasmus MC, Rotterdam, Netherlands
    Department of Clinical Genetics, Erasmus MC, Rotterdam, Netherlands
  • Anna Sanyiwa
    Department of Ophthalmology, Muhimbili Universtiy of Health and Allied Sciences, Dar es Salaam, Tanzania, United Republic of
  • Hassan G Hassan
    Department of Ophthalmology, Comprehensive Community Based Rehabilitation in Tanzania (CCBRT) Hospital, Dar es Salaam, Tanzania, United Republic of
  • Heiko Philippin
    Department of Ophthalmology, Kilimanjaro Christian Medical Centre, Moshi, Tanzania, United Republic of
  • Colin Cook
    Division of Ophthalmology, University of Cape Town, Cape Town, South Africa
  • Janey L Wiggs
    Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, United States
  • Christopher J Hammond
    Department of Twin Research and Genetic Epidemiology, King's College London, London, United Kingdom
  • Michael A Hauser
    Department of Ophthalmology & Medicine, Duke University, Durham, North Carolina, United States
  • Hans G Lemij
    Glaucoma Service, The Rotterdam Eye Hospital, Rotterdam, Netherlands
  • Ruth Loos
    The Charles Bronfman Institute of Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, United States
    The Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, New York, United States
  • Cornelia van Duijn
    Department of Epidemiology, Erasmus MC, Rotterdam, Netherlands
  • Alberta A H J Thiadens
    Department of Ophthalmology & Epidemiology, Erasmus MC, Rotterdam, Netherlands
  • Caroline C W Klaver
    Department of Ophthalmology & Epidemiology, Erasmus MC, Rotterdam, Netherlands
    Department of Ophthalmology, Radboud Universty Medical Center, Nijmegen, Netherlands
  • Footnotes
    Commercial Relationships   Pieter Bonnemaijer, None; Adriana I Iglesias, None; Anna Sanyiwa, None; Hassan Hassan, None; Heiko Philippin, None; Colin Cook, None; Janey Wiggs, None; Christopher Hammond, None; Michael Hauser, None; Hans Lemij, None; Ruth Loos, None; Cornelia van Duijn, None; Alberta Thiadens, None; Caroline Klaver, None
  • Footnotes
    Support  Combined Ophthalmic Research Rotterdam (CORR), BrightFocus Foundation, Algemene Nederlandse Vereniging ter Voorkoming van blindheid, Landelijke Stichting voor Blinden en Slechtzienden, Stichting Beheer het Schild, Prof dr Henkes stichting, Rotterdamse Stichting Blindenbelangen, Stichting Glaucoomfonds, National Institute for Health Research (NIHR) Senior Research Fellowship to CJH,The Mount Sinai BioMe Biobank Program is supported by The Andrea and Charles Bronfman Philanthropies and, partially by a grant from NHGRI (U01HG007417), Ruth loos is funded by NIDDK (R01DK110113, R01DK101855, R01DK107786) and NHGRI (U01HG007417).
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 5136. doi:
  • Views
  • Share
  • Tools
    • Alerts
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Pieter W.M. Bonnemaijer, Adriana I Iglesias, Anna Sanyiwa, Hassan G Hassan, Heiko Philippin, Colin Cook, Janey L Wiggs, Christopher J Hammond, Michael A Hauser, Hans G Lemij, Ruth Loos, Cornelia van Duijn, Alberta A H J Thiadens, Caroline C W Klaver; Genome-wide association study of primary open-angle glaucoma in continental and admixed African populations.. Invest. Ophthalmol. Vis. Sci. 2018;59(9):5136.

      Download citation file:

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

  • Supplements

Purpose : Primary open-angle glaucoma (POAG) is the predominant type of glaucoma worldwide. Its prevalence varies greatly among ethnic groups, and is the highest in Black African populations (2-7%). So far worldwide efforts to elucidate the genetic complexity of POAG in African populations has been very limited. To fill this gap, we conducted a genome wide-association study (GWAS) for POAG in individuals of African ancestry from the GIGA study and the BioMe biobank.

Methods : 1113 POAG cases and 1826 controls collected from Tanzania, South Africa and African Americans from the USA were genotyped on either the Illumina HumanOmniExpressExome or HumanOmni2.5Exome Beadchip. Genotypes were imputed to 1000 Genomes reference panel. The association between genotypes and susceptibility to POAG was tested using logistic regression assuming an additive genetic model, adjusting for age, sex and ethnic substructure. Top SNPs (P < 1 x 10-6) from the discovery stage were followed up in a replication comprising four independent studies from South African, Ghanian, Nigerian and African American descent (Eyes of Africa Genetic Consortium and the South London POAG case –control cohort comprising individuals of West African origin.

Results : First, we tested the association with 15 previously reported POAG SNPs. Using a local replication approach, we queried all SNPs within strong linkage disequilibrium (R2>0.8, European LD), and observed nominal significance (P<0.05) for three SNPs located in the TXNRD2, CDKN2B-AS1, and TMCO1 region. rs16984299 in TXNRD2, remained significant after correction for multiple testing (PBonferonni=0.049). A genetic risk score combining the known POAG loci was significantly associated with POAG in the GIGA study (OR, 1.56; 95%CI, 1.26-1.93;P=4.79 x 10-5). Second, by genome-wide association testing we identified one novel locus, rs141186647 in EXOC4 , reaching genome-wide significance in the discovery stage. Replication in four predominantly West African ancestral studies was unsuccessful mostly due to high degree of genetic heterogeneity observed at this locus.

Conclusions : We conducted the first GWAS of POAG in continental Africans. We verified the European glaucoma gene TXNRD2, and identified a novel locus encompassing EXOC4. A genetic risk score showed that the combined effect of the known loci from European/Asian GWAS was associated with POAG in Africans.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.


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.