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 Type:	Refereed Article
Keywords:	glaucoma, genetics
Research Division:	Biomedical and Clinical Sciences
Research Group:	Ophthalmology and optometry
Research Field:	Ophthalmology
Objective Division:	Health
Objective Group:	Clinical health
Objective Field:	Clinical health not elsewhere classified
UTAS Author:	Burdon, KP (Professor Kathryn Burdon)
UTAS Author:	Hewitt, AW (Professor Alex Hewitt)
ID Code:	118009
Year Published:	2017
Web of Science® Times Cited:	76
Deposited By:	Menzies Institute for Medical Research
Deposited On:	2017-06-30
Last Modified:	2022-08-25
Downloads:	0