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Common genetic variants near the brittle cornea syndrome locus ZNF469 influence the blinding disease risk factor central corneal thickness


Lu, Y and Dimasi, DP and Hysi, PG and Hewitt, AW and Burdon, KP and Toh, T and Ruddle, JB and Li, YJ and Mitchell, P and Healey, PR and Montgomery, GW and Hansell, N and Spector, TD and Martin, NG and Young, TL and Hammond, CJ and Macgregor, S and Craig, JE and Mackey, DA, Common genetic variants near the brittle cornea syndrome locus ZNF469 influence the blinding disease risk factor central corneal thickness, PL o S Genetics (Print), 6, (5) Article e1000947. ISSN 1553-7390 (2010) [Refereed Article]


Copyright Statement

Copyright 2010 The Authors-this article is distributed under the terms of the Creative Commons Attribution 3.0

DOI: doi:10.1371/journal.pgen.1000947


Central corneal thickness (CCT), one of the most highly heritable human traits (h2typically>0.9), is important for the diagnosis of glaucoma and a potential risk factor for glaucoma susceptibility. We conducted genome-wide association studies in five cohorts from Australia and the United Kingdom (total N = 5058). Three cohorts were based on individually genotyped twin collections, with the remaining two cohorts genotyped on pooled samples from singletons with extreme trait values. The pooled sample findings were validated by individual genotyping the pooled samples together with additional samples also within extreme quantiles. We describe methods for efficient combined analysis of the results from these different study designs. We have identified and replicated quantitative trait loci on chromosomes 13 and 16 for association with CCT. The locus on chromosome 13 (nearest gene FOXO1) had an overall meta-analysis p-value for all the individually genotyped samples of 4.66 10-10. The locus on chromosome 16 was associated with CCT with p = 8.95 10 -11. The nearest gene to the associated chromosome 16 SNPs was ZNF469, a locus recently implicated in Brittle Cornea Syndrome (BCS), a very rare disorder characterized by abnormal thin corneas. Our findings suggest that in addition to rare variants in ZNF469 underlying CCT variation in BCS patients, more common variants near this gene may contribute to CCT variation in the general population.

Item Details

Item Type:Refereed Article
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:Hewitt, AW (Professor Alex Hewitt)
UTAS Author:Burdon, KP (Professor Kathryn Burdon)
UTAS Author:Mackey, DA (Professor David Mackey)
ID Code:91365
Year Published:2010
Web of Science® Times Cited:111
Deposited By:Menzies Institute for Medical Research
Deposited On:2014-05-15
Last Modified:2016-11-16
Downloads:300 View Download Statistics

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