Human Genetics

, Volume 133, Issue 1, pp 41–57

Genome-wide association study and meta-analysis of intraocular pressure

  • A. Bilge Ozel
  • Sayoko E. Moroi
  • David M. Reed
  • Melisa Nika
  • Caroline M. Schmidt
  • Sara Akbari
  • Kathleen Scott
  • Frank Rozsa
  • Hemant Pawar
  • David C. Musch
  • Paul R. Lichter
  • Doug Gaasterland
  • Kari Branham
  • Jesse Gilbert
  • Sarah J. Garnai
  • Wei Chen
  • Mohammad Othman
  • John Heckenlively
  • Anand Swaroop
  • Gonçalo Abecasis
  • David S. Friedman
  • Don Zack
  • Allison Ashley-Koch
  • Megan Ulmer
  • Jae H. Kang
  • NEIGHBOR Consortium
  • Yutao Liu
  • Brian L. Yaspan
  • Jonathan Haines
  • R. Rand Allingham
  • Michael A. Hauser
  • Louis Pasquale
  • Janey Wiggs
  • Julia E. Richards
  • Jun Z. Li
Original Investigation

DOI: 10.1007/s00439-013-1349-5

Cite this article as:
Ozel, A.B., Moroi, S.E., Reed, D.M. et al. Hum Genet (2014) 133: 41. doi:10.1007/s00439-013-1349-5

Abstract

Elevated intraocular pressure (IOP) is a major risk factor for glaucoma and is influenced by genetic and environmental factors. Recent genome-wide association studies (GWAS) reported associations with IOP at TMCO1 and GAS7, and with primary open-angle glaucoma (POAG) at CDKN2B-AS1, CAV1/CAV2, and SIX1/SIX6. To identify novel genetic variants and replicate the published findings, we performed GWAS and meta-analysis of IOP in >6,000 subjects of European ancestry collected in three datasets: the NEI Glaucoma Human genetics collaBORation, GLAUcoma Genes and ENvironment study, and a subset of the Age-related Macular Degeneration-Michigan, Mayo, AREDS and Pennsylvania study. While no signal achieved genome-wide significance in individual datasets, a meta-analysis identified significant associations with IOP at TMCO1 (rs7518099-G, p = 8.0 × 10−8). Focused analyses of five loci previously reported for IOP and/or POAG, i.e., TMCO1, CDKN2B-AS1, GAS7, CAV1/CAV2, and SIX1/SIX6, revealed associations with IOP that were largely consistent across our three datasets, and replicated the previously reported associations in both effect size and direction. These results confirm the involvement of common variants in multiple genomic regions in regulating IOP and/or glaucoma risk.

Supplementary material

439_2013_1349_MOESM1_ESM.pdf (1.2 mb)
Supplementary material 1 (PDF 1179 kb)

Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • A. Bilge Ozel
    • 1
  • Sayoko E. Moroi
    • 2
  • David M. Reed
    • 2
  • Melisa Nika
    • 2
  • Caroline M. Schmidt
    • 2
  • Sara Akbari
    • 2
  • Kathleen Scott
    • 2
  • Frank Rozsa
    • 2
  • Hemant Pawar
    • 2
  • David C. Musch
    • 2
    • 3
  • Paul R. Lichter
    • 2
  • Doug Gaasterland
    • 4
  • Kari Branham
    • 2
  • Jesse Gilbert
    • 2
  • Sarah J. Garnai
    • 2
  • Wei Chen
    • 5
    • 6
  • Mohammad Othman
    • 2
  • John Heckenlively
    • 2
  • Anand Swaroop
    • 7
  • Gonçalo Abecasis
    • 8
  • David S. Friedman
    • 9
  • Don Zack
    • 9
  • Allison Ashley-Koch
    • 10
  • Megan Ulmer
    • 10
  • Jae H. Kang
    • 11
  • NEIGHBOR Consortium
  • Yutao Liu
    • 10
  • Brian L. Yaspan
    • 12
  • Jonathan Haines
    • 12
  • R. Rand Allingham
    • 10
  • Michael A. Hauser
    • 10
  • Louis Pasquale
    • 11
    • 13
  • Janey Wiggs
    • 13
  • Julia E. Richards
    • 2
    • 3
  • Jun Z. Li
    • 1
  1. 1.Department of Human GeneticsUniversity of MichiganAnn ArborUSA
  2. 2.Department of Ophthalmology and Visual SciencesUniversity of MichiganAnn ArborUSA
  3. 3.Department of EpidemiologyUniversity of MichiganAnn ArborUSA
  4. 4.Eye Doctors of Washington DCWashingtonUSA
  5. 5.Division of Pulmonary Medicine, Allergy and Immunology, Children’s Hospital of PittsburghUniversity of Pittsburgh Medical SchoolPittsburghUSA
  6. 6.Departments of Biostatistics and Human GeneticsUniversity of PittsburghPittsburghUSA
  7. 7.National Eye InstituteNational Institutes of HealthBethesdaUSA
  8. 8.Department of BiostatisticsUniversity of MichiganAnn ArborUSA
  9. 9.Department of OphthalmologyJohns Hopkins University School of MedicineBaltimoreUSA
  10. 10.Center for Human GeneticsDuke University School of MedicineDurhamUSA
  11. 11.Channing Division of Network MedicineBrigham and Women’s HospitalBostonUSA
  12. 12.Center for Human Genetics ResearchVanderbilt University School of MedicineNashvilleUSA
  13. 13.Department of Ophthalmology, Harvard Medical SchoolMassachusetts Eye and Ear InfirmaryBostonUSA

Personalised recommendations