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GWAS-by-subtraction reveals an IOP-independent component of primary open angle glaucoma

Author

Listed:
  • Yu Huang

    (Southern Medical University
    Guangdong Academy of Medical Sciences
    Ninewells Hospital and Medical School)

  • Denis Plotnikov

    (Kazan State Medical University
    Cardiff University)

  • Huan Wang

    (Ninewells Hospital and Medical School)

  • Danli Shi

    (The Hong Kong Polytechnic University)

  • Cong Li

    (Southern Medical University)

  • Xueli Zhang

    (Southern Medical University)

  • Xiayin Zhang

    (Southern Medical University)

  • Shulin Tang

    (Southern Medical University)

  • Xianwen Shang

    (Southern Medical University
    Guangdong Academy of Medical Sciences
    Centre for Eye Research Australia)

  • Yijun Hu

    (Southern Medical University)

  • Honghua Yu

    (Southern Medical University)

  • Hongyang Zhang

    (Southern Medical University)

  • Jeremy A. Guggenheim

    (Cardiff University)

  • Mingguang He

    (Southern Medical University
    The Hong Kong Polytechnic University)

Abstract

The etiology of primary open angle glaucoma is constituted by both intraocular pressure-dependent and intraocular pressure-independent mechanisms. However, GWASs of traits affecting primary open angle glaucoma through mechanisms independent of intraocular pressure remains limited. Here, we address this gap by subtracting the genetic effects of a GWAS for intraocular pressure from a GWAS for primary open angle glaucoma to reveal the genetic contribution to primary open angle glaucoma via intraocular pressure-independent mechanisms. Seventeen independent genome-wide significant SNPs were associated with the intraocular pressure-independent component of primary open angle glaucoma. Of these, 7 are located outside known normal tension glaucoma loci, 11 are located outside known intraocular pressure loci, and 2 are novel primary open angle glaucoma loci. The intraocular pressure-independent genetic component of primary open angle glaucoma is associated with glaucoma endophenotypes, while the intraocular pressure-dependent component is associated with blood pressure and vascular permeability. A genetic risk score for the intraocular pressure-independent component of primary open angle glaucoma is associated with 26 different retinal micro-vascular features, which contrasts with the genetic risk score for the intraocular pressure-dependent component. Increased understanding of these intraocular pressure-dependent and intraocular pressure-independent components provides insights into the pathogenesis of glaucoma.

Suggested Citation

  • Yu Huang & Denis Plotnikov & Huan Wang & Danli Shi & Cong Li & Xueli Zhang & Xiayin Zhang & Shulin Tang & Xianwen Shang & Yijun Hu & Honghua Yu & Hongyang Zhang & Jeremy A. Guggenheim & Mingguang He, 2024. "GWAS-by-subtraction reveals an IOP-independent component of primary open angle glaucoma," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-53331-0
    DOI: 10.1038/s41467-024-53331-0
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