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

Aung, T, Ozaki, M, Khor, CC, Burdon, KP ORCID: 0000-0001-8217-1249 and Hewitt, AW ORCID: 0000-0002-5123-5999 2017 , 'Genetic association study of exfoliation syndrome identifies a protective rare variant at LOXL1 and five new susceptibility loci' , Nature Genetics, vol. 49, no. 7 , pp. 993-1004 , doi: 10.1038/ng.3875.

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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 -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: Article
Authors/Creators:Aung, T and Ozaki, M and Khor, CC and Burdon, KP and Hewitt, AW
Keywords: glaucoma, genetics
Journal or Publication Title: Nature Genetics
Publisher: Nature Publishing Group
ISSN: 1061-4036
DOI / ID Number: 10.1038/ng.3875
Copyright Information:

© 2017 Nature America

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