Genome-wide analyses identify 68 new loci associated with intraocular pressure and improve risk prediction for primary open-angle glaucoma

UK Biobank Eye and Vision Consortium, NEIGHBORHOOD Consortium

Research output: Contribution to journalArticle

Abstract

Glaucoma is the leading cause of irreversible blindness globally1. Despite its gravity, the disease is frequently undiagnosed in the community2. Raised intraocular pressure (IOP) is the most important risk factor for primary open-angle glaucoma (POAG)3,4. Here we present a meta-analysis of 139,555 European participants, which identified 112 genomic loci associated with IOP, 68 of which are novel. These loci suggest a strong role for angiopoietin-receptor tyrosine kinase signaling, lipid metabolism, mitochondrial function and developmental processes underlying risk for elevated IOP. In addition, 48 of these loci were nominally associated with glaucoma in an independent cohort, 14 of which were significant at a Bonferroni-corrected threshold. Regression-based glaucoma-prediction models had an area under the receiver operating characteristic curve (AUROC) of 0.76 in US NEIGHBORHOOD study participants and 0.74 in independent glaucoma cases from the UK Biobank. Genetic-prediction models for POAG offer an opportunity to target screening and timely therapy to individuals most at risk.

Original languageEnglish (US)
Pages (from-to)1-5
Number of pages5
JournalNature Genetics
DOIs
StateAccepted/In press - May 21 2018

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Intraocular Pressure
Glaucoma
Genome
Angiopoietins
Genetic Models
Gravitation
Receptor Protein-Tyrosine Kinases
Blindness
Lipid Metabolism
ROC Curve
Meta-Analysis
Primary Open Angle Glaucoma
Therapeutics

ASJC Scopus subject areas

  • Genetics

Cite this

Genome-wide analyses identify 68 new loci associated with intraocular pressure and improve risk prediction for primary open-angle glaucoma. / UK Biobank Eye and Vision Consortium; NEIGHBORHOOD Consortium.

In: Nature Genetics, 21.05.2018, p. 1-5.

Research output: Contribution to journalArticle

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abstract = "Glaucoma is the leading cause of irreversible blindness globally1. Despite its gravity, the disease is frequently undiagnosed in the community2. Raised intraocular pressure (IOP) is the most important risk factor for primary open-angle glaucoma (POAG)3,4. Here we present a meta-analysis of 139,555 European participants, which identified 112 genomic loci associated with IOP, 68 of which are novel. These loci suggest a strong role for angiopoietin-receptor tyrosine kinase signaling, lipid metabolism, mitochondrial function and developmental processes underlying risk for elevated IOP. In addition, 48 of these loci were nominally associated with glaucoma in an independent cohort, 14 of which were significant at a Bonferroni-corrected threshold. Regression-based glaucoma-prediction models had an area under the receiver operating characteristic curve (AUROC) of 0.76 in US NEIGHBORHOOD study participants and 0.74 in independent glaucoma cases from the UK Biobank. Genetic-prediction models for POAG offer an opportunity to target screening and timely therapy to individuals most at risk.",
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