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| PMID |
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| TITLE |
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| WNT10A exonic variant increases the risk of keratoconus by decreasing corneal thickness. |
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| ABSTRACT |
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| Keratoconus is a degenerative eye condition which results from thinning of the cornea and causes vision distortion. Treatments such as ultraviolet (UV) cross-linking have proved effective for management of keratoconus when performed in early stages of the disease. The central corneal thickness (CCT) is a highly heritable endophenotype of keratoconus, and it is estimated that up to 95% of its phenotypic variance is due to genetics. Genome-wide association efforts of CCT have identified common variants (i.e. minor allele frequency (MAF) >5%). However, these studies typically ignore the large set of exonic variants whose MAF is usually low. In this study, we performed a CCT exome-wide association analysis in a sample of 1029 individuals from a population-based study in Western Australia. We identified a genome-wide significant exonic variant rs121908120 (P = 6.63 × 10(-10)) in WNT10A. This gene is 437 kb from a gene previously associated with CCT (USP37). We showed in a conditional analysis that the WNT10A variant completely accounts for the signal previously seen at USP37. We replicated our finding in independent samples from the Brisbane Adolescent Twin Study, Twin Eye Study in Tasmania and the Rotterdam Study. Further, we genotyped rs121908120 in 621 keratoconus cases and compared the frequency to a sample of 1680 unscreened controls from the Queensland Twin Registry. We found that rs121908120 increases the risk of keratoconus two times (odds ratio 2.03, P = 5.41 × 10(-5)). |
| © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com. |
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| DATE PUBLISHED |
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| HISTORY |
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| PUBSTATUS |
PUBSTATUSDATE |
| received |
2015/03/02 |
| accepted |
2015/06/02 |
| aheadofprint |
2015/06/05 |
| entrez |
2015/06/07 06:00 |
| pubmed |
2015/06/07 06:00 |
| medline |
2015/06/07 06:00 |
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| AUTHORS |
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| NAME |
COLLECTIVENAME |
LASTNAME |
FORENAME |
INITIALS |
AFFILIATION |
AFFILIATIONINFO |
| Cuellar-Partida G |
|
Cuellar-Partida |
Gabriel |
G |
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Statistical Genetics, QIMR Berghofer Medical Research Institute, Brisbane, Australia. |
| Springelkamp H |
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Springelkamp |
Henriët |
H |
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Department of Ophthalmology, Department of Epidemiology. |
| Lucas SE |
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Lucas |
Sionne E M |
SE |
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Menzies Institute for Medical Research. |
| Yazar S |
|
Yazar |
Seyhan |
S |
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Centre for Ophthalmology and Visual Science, Lions Eye Institute, University of Western Australia. |
| Hewitt AW |
|
Hewitt |
Alex W |
AW |
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School of Medicine, Menzies Research Institute Tasmania, University of Tasmania, Hobart, Australia, Centre for Eye Research Australia, Melbourne University, Melbourne, Australia. |
| Iglesias AI |
|
Iglesias |
Adriana I |
AI |
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Department of Ophthalmology, Department of Epidemiology. |
| Montgomery GW |
|
Montgomery |
Grant W |
GW |
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Molecular Epidemiology. |
| Martin NG |
|
Martin |
Nicholas G |
NG |
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Genetic Epidemiology, QIMR Berghofer Medical Research Institute, Brisbane, Australia and. |
| Pennell CE |
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Pennell |
Craig E |
CE |
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School of Women's and Infants' Health, University of Western Australia, Perth, Australia. |
| van Leeuwen EM |
|
van Leeuwen |
Elisabeth M |
EM |
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Department of Epidemiology. |
| Verhoeven VJ |
|
Verhoeven |
Virginie J M |
VJ |
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Department of Ophthalmology, Department of Epidemiology. |
| Hofman A |
|
Hofman |
Albert |
A |
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Department of Epidemiology, Netherlands Consortium for Healthy Ageing, Netherlands Genomics Initiative, the Hague 2593 CE, The Netherlands. |
| Uitterlinden AG |
|
Uitterlinden |
André G |
AG |
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Department of Epidemiology, Department of Internal Medicine, Erasmus Medical Center, Rotterdam 3000 CA, The Netherlands, Netherlands Consortium for Healthy Ageing, Netherlands Genomics Initiative, the Hague 2593 CE, The Netherlands. |
| Ramdas WD |
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Ramdas |
Wishal D |
WD |
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Department of Ophthalmology. |
| Wolfs RC |
|
Wolfs |
Roger C W |
RC |
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Department of Ophthalmology. |
| Vingerling JR |
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Vingerling |
Johannes R |
JR |
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Department of Ophthalmology, Department of Epidemiology. |
| Brown MA |
|
Brown |
Matthew A |
MA |
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University of Queensland Diamantina Institute, Translational Research Institute, Princess Alexandra Hospital, Brisbane, Australia. |
| Mills RA |
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Mills |
Richard A |
RA |
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Department of Ophthalmology, Flinders University, Adelaide, SA, Australia. |
| Craig JE |
|
Craig |
Jamie E |
JE |
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Department of Ophthalmology, Flinders University, Adelaide, SA, Australia. |
| Klaver CC |
|
Klaver |
Caroline C W |
CC |
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Department of Ophthalmology, Department of Epidemiology. |
| van Duijn CM |
|
van Duijn |
Cornelia M |
CM |
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Department of Epidemiology. |
| Burdon KP |
|
Burdon |
Kathryn P |
KP |
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Menzies Institute for Medical Research. |
| MacGregor S |
|
MacGregor |
Stuart |
S |
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Statistical Genetics, QIMR Berghofer Medical Research Institute, Brisbane, Australia, stuart.macgregor@qimrberghofer.edu.au. |
| Mackey DA |
|
Mackey |
David A |
DA |
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Centre for Ophthalmology and Visual Science, Lions Eye Institute, University of Western Australia. |
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| INVESTIGATORS |
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| JOURNAL |
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| VOLUME: 24 |
| ISSUE: 17 |
| TITLE: Human molecular genetics |
| ISOABBREVIATION: Hum. Mol. Genet. |
| YEAR: 2015 |
| MONTH: Sep |
| DAY: 1 |
| MEDLINEDATE: |
| SEASON: |
| CITEDMEDIUM: Internet |
| ISSN: 1460-2083 |
| ISSNTYPE: Electronic |
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| MEDLINE JOURNAL |
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| MEDLINETA: Hum Mol Genet |
| COUNTRY: England |
| ISSNLINKING: 0964-6906 |
| NLMUNIQUEID: 9208958 |
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| PUBLICATION TYPE |
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| PUBLICATIONTYPE TEXT |
| Journal Article |
| Research Support, Non-U.S. Gov't |
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