Common genetic variants near the Brittle Cornea Syndrome locus ZNF469 influence the blinding disease risk factor central corneal thickness.
Central corneal thickness (CCT), one of the most highly heritable human traits (h(2) typically>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 Kingd...
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doaj-99e1c7bb125743df91c7a154f6832d642020-11-25T01:57:37ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042010-05-0165e100094710.1371/journal.pgen.1000947Common genetic variants near the Brittle Cornea Syndrome locus ZNF469 influence the blinding disease risk factor central corneal thickness.Yi LuDavid P DimasiPirro G HysiAlex W HewittKathryn P BurdonTze'Yo TohJonathan B RuddleYi Ju LiPaul MitchellPaul R HealeyGrant W MontgomeryNarelle HansellTimothy D SpectorNicholas G MartinTerri L YoungChristopher J HammondStuart MacgregorJamie E CraigDavid A MackeyCentral corneal thickness (CCT), one of the most highly heritable human traits (h(2) typically>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 4.6x10(-10). The locus on chromosome 16 was associated with CCT with p = 8.95x10(-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.http://europepmc.org/articles/PMC2869325?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Yi Lu David P Dimasi Pirro G Hysi Alex W Hewitt Kathryn P Burdon Tze'Yo Toh Jonathan B Ruddle Yi Ju Li Paul Mitchell Paul R Healey Grant W Montgomery Narelle Hansell Timothy D Spector Nicholas G Martin Terri L Young Christopher J Hammond Stuart Macgregor Jamie E Craig David A Mackey |
spellingShingle |
Yi Lu David P Dimasi Pirro G Hysi Alex W Hewitt Kathryn P Burdon Tze'Yo Toh Jonathan B Ruddle Yi Ju Li Paul Mitchell Paul R Healey Grant W Montgomery Narelle Hansell Timothy D Spector Nicholas G Martin Terri L Young Christopher J Hammond Stuart Macgregor Jamie E Craig David A Mackey Common genetic variants near the Brittle Cornea Syndrome locus ZNF469 influence the blinding disease risk factor central corneal thickness. PLoS Genetics |
author_facet |
Yi Lu David P Dimasi Pirro G Hysi Alex W Hewitt Kathryn P Burdon Tze'Yo Toh Jonathan B Ruddle Yi Ju Li Paul Mitchell Paul R Healey Grant W Montgomery Narelle Hansell Timothy D Spector Nicholas G Martin Terri L Young Christopher J Hammond Stuart Macgregor Jamie E Craig David A Mackey |
author_sort |
Yi Lu |
title |
Common genetic variants near the Brittle Cornea Syndrome locus ZNF469 influence the blinding disease risk factor central corneal thickness. |
title_short |
Common genetic variants near the Brittle Cornea Syndrome locus ZNF469 influence the blinding disease risk factor central corneal thickness. |
title_full |
Common genetic variants near the Brittle Cornea Syndrome locus ZNF469 influence the blinding disease risk factor central corneal thickness. |
title_fullStr |
Common genetic variants near the Brittle Cornea Syndrome locus ZNF469 influence the blinding disease risk factor central corneal thickness. |
title_full_unstemmed |
Common genetic variants near the Brittle Cornea Syndrome locus ZNF469 influence the blinding disease risk factor central corneal thickness. |
title_sort |
common genetic variants near the brittle cornea syndrome locus znf469 influence the blinding disease risk factor central corneal thickness. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS Genetics |
issn |
1553-7390 1553-7404 |
publishDate |
2010-05-01 |
description |
Central corneal thickness (CCT), one of the most highly heritable human traits (h(2) typically>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 4.6x10(-10). The locus on chromosome 16 was associated with CCT with p = 8.95x10(-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. |
url |
http://europepmc.org/articles/PMC2869325?pdf=render |
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