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Genome-wide meta-analysis identifies 22 loci for normal tension glaucoma with significant overlap with high tension glaucoma

Author

Listed:
  • Santiago Diaz-Torres

    (QIMR Berghofer Medical Research Institute
    University of Queensland (UQ))

  • Weixiong He

    (QIMR Berghofer Medical Research Institute
    University of Queensland (UQ))

  • Regina Yu

    (QIMR Berghofer Medical Research Institute)

  • Anthony P. Khawaja

    (Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology)

  • Christopher J. Hammond

    (King’s College London
    King’s College London)

  • Pirro G. Hysi

    (King’s College London
    King’s College London)

  • Louis R. Pasquale

    (Icahn School of Medicine at Mount Sinai)

  • Yeda Wu

    (QIMR Berghofer Medical Research Institute)

  • Michiaki Kubo

    (RIKEN Center for Integrative Medical Sciences)

  • Masato Akiyama

    (RIKEN Center for Integrative Medical Sciences
    Kyushu University)

  • Tin Aung

    (Duke-NUS Medical School
    National University of Singapore)

  • Ching-Yu Cheng

    (Duke-NUS Medical School
    National University of Singapore)

  • Chiea Chuen Khor

    (Genome Institute of Singapore)

  • Peter Kraft

    (Harvard School of Public Health)

  • Jae H. Kang

    (Harvard Medical School)

  • Alex W. Hewitt

    (University of Tasmania)

  • David A. Mackey

    (Lions Eye Institute)

  • Jamie E. Craig

    (Flinders Medical Centre)

  • Janey L. Wiggs

    (Harvard Medical School)

  • Jue-Sheng Ong

    (QIMR Berghofer Medical Research Institute)

  • Stuart MacGregor

    (QIMR Berghofer Medical Research Institute
    University of Queensland (UQ))

  • Puya Gharahkhani

    (QIMR Berghofer Medical Research Institute
    University of Queensland (UQ)
    Queensland University of Technology (QUT))

Abstract

Primary open-angle glaucoma typically presents as two subtypes. This study aimed to elucidate the shared and distinct genetic architectures of normal-tension (NTG) and high-tension glaucoma (HTG), motivated by the need to develop intraocular pressure (IOP)-independent drug targets for the disease. We conducted a comprehensive multi-ethnic meta-analysis, prioritized variants based on functional annotation, and explored drug-gene interactions. We further assessed the genetic overlap between NTG and HTG using pairwise GWAS analysis. We identified 22 risk loci associated with NTG, 17 of which have not previously been reported for NTG. Two loci, BMP4 and TBKBP1, have not previously been associated with glaucoma at the genome-wide significance level. Our results indicate that while there is a significant overlap in risk loci between tension subtypes, the magnitude of the effect tends to be lower in NTG compared to HTG, particularly for IOP-related loci. Additionally, we identified a potential role for biologic immunomodulatory treatments as neuroprotective agents.

Suggested Citation

  • Santiago Diaz-Torres & Weixiong He & Regina Yu & Anthony P. Khawaja & Christopher J. Hammond & Pirro G. Hysi & Louis R. Pasquale & Yeda Wu & Michiaki Kubo & Masato Akiyama & Tin Aung & Ching-Yu Cheng , 2024. "Genome-wide meta-analysis identifies 22 loci for normal tension glaucoma with significant overlap with high tension glaucoma," Nature Communications, Nature, vol. 15(1), pages 1-9, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-54301-2
    DOI: 10.1038/s41467-024-54301-2
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    1. Adrián I. Campos & Luis M. García-Marín & Enda M. Byrne & Nicholas G. Martin & Gabriel Cuéllar-Partida & Miguel E. Rentería, 2020. "Insights into the aetiology of snoring from observational and genetic investigations in the UK Biobank," Nature Communications, Nature, vol. 11(1), pages 1-12, December.
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