Genome-wide Meta-analysis Identifies 22 Loci for Normal Tension Glaucoma with Significant Overlap with High Tension Glaucoma

Overview

Journal Nat Commun

Specialty Biology

Date 2024 Nov 17

PMID 39551815

Authors

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

Chiea Chuen Khor

Peter Kraft

Jae H Kang

Alex W Hewitt

David A Mackey

Jamie E Craig

Janey L Wiggs

Jue-Sheng Ong

Stuart Macgregor

Puya Gharahkhani

Affiliations

Soon will be listed here.

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.

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