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Genetic association study of exfoliation syndrome identifies a protective rare variant at LOXL1 and five new susceptibility loci

Citation

Aung, T and Ozaki, M and Khor, CC and Burdon, KP and Hewitt, AW, et al, Genetic association study of exfoliation syndrome identifies a protective rare variant at LOXL1 and five new susceptibility loci, Nature Genetics, 49, (7) pp. 993-1004. ISSN 1061-4036 (2017) [Refereed Article]

Copyright Statement

2017 Nature America

DOI: doi:10.1038/ng.3875

Abstract

Exfoliation syndrome (XFS) is the most common known risk factor for secondary glaucoma and a major cause of blindness worldwide. Variants in two genes, LOXL1 and CACNA1A, have previously been associated with XFS. To further elucidate the genetic basis of XFS, we collected a global sample of XFS cases to refine the association at LOXL1, which previously showed inconsistent results across populations, and to identify new variants associated with XFS. We identified a rare protective allele at LOXL1 (p.Phe407, odds ratio (OR) = 25, P = 2.9 10-14) through deep resequencing of XFS cases and controls from nine countries. A genome-wide association study (GWAS) of XFS cases and controls from 24 countries followed by replication in 18 countries identified seven genome-wide significant loci (P < 5 10-8). We identified association signals at 13q12 (POMP), 11q23.3 (TMEM136), 6p21 (AGPAT1), 3p24 (RBMS3) and 5q23 (near SEMA6A). These findings provide biological insights into the pathology of XFS and highlight a potential role for naturally occurring rare LOXL1 variants in disease biology.

Item Details

Item Type:Refereed Article
Keywords:glaucoma, genetics
Research Division:Medical and Health Sciences
Research Group:Ophthalmology and Optometry
Research Field:Ophthalmology
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Hearing, Vision, Speech and Their Disorders
Author:Burdon, KP (Associate Professor Kathryn Burdon)
Author:Hewitt, AW (Professor Alex Hewitt)
ID Code:118009
Year Published:2017
Web of Science® Times Cited:7
Deposited By:Menzies Institute for Medical Research
Deposited On:2017-06-30
Last Modified:2018-06-06
Downloads:0

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