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

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posted on 2023-05-18, 00:42 authored by Lu, Y, Dimasi, DP, Hysi, PG, Alexander HewittAlexander Hewitt, Kathryn BurdonKathryn Burdon, Toh, T, Ruddle, JB, Li, YJ, Mitchell, P, Healey, PR, Montgomery, GW, Hansell, N, Spector, TD, Martin, NG, Young, TL, Hammond, CJ, Macgregor, S, Craig, JE, David MackeyDavid Mackey
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.


Publication title

PL o S Genetics (Print)





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Menzies Institute for Medical Research


Public Library of Science

Place of publication

United States

Rights statement

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

Repository Status

  • Open

Socio-economic Objectives

Clinical health not elsewhere classified

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