Genetic Epidemiology, Psychiatric Genetics, Asthma Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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PMID
26049155
TITLE
WNT10A exonic variant increases the risk of keratoconus by decreasing corneal thickness.
ABSTRACT
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.
DATE PUBLISHED
2015 Sep 1
HISTORY
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
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Cuellar-Partida G Cuellar-Partida Gabriel G Statistical Genetics, QIMR Berghofer Medical Research Institute, Brisbane, Australia.
Springelkamp H Springelkamp Henriët H Department of Ophthalmology, Department of Epidemiology.
Lucas SE Lucas Sionne E M SE Menzies Institute for Medical Research.
Yazar S Yazar Seyhan S Centre for Ophthalmology and Visual Science, Lions Eye Institute, University of Western Australia.
Hewitt AW Hewitt Alex W AW 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 Department of Ophthalmology, Department of Epidemiology.
Montgomery GW Montgomery Grant W GW Molecular Epidemiology.
Martin NG Martin Nicholas G NG Genetic Epidemiology, QIMR Berghofer Medical Research Institute, Brisbane, Australia and.
Pennell CE Pennell Craig E CE School of Women's and Infants' Health, University of Western Australia, Perth, Australia.
van Leeuwen EM van Leeuwen Elisabeth M EM Department of Epidemiology.
Verhoeven VJ Verhoeven Virginie J M VJ Department of Ophthalmology, Department of Epidemiology.
Hofman A Hofman Albert A Department of Epidemiology, Netherlands Consortium for Healthy Ageing, Netherlands Genomics Initiative, the Hague 2593 CE, The Netherlands.
Uitterlinden AG Uitterlinden André G AG 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 Ramdas Wishal D WD Department of Ophthalmology.
Wolfs RC Wolfs Roger C W RC Department of Ophthalmology.
Vingerling JR Vingerling Johannes R JR Department of Ophthalmology, Department of Epidemiology.
Brown MA Brown Matthew A MA University of Queensland Diamantina Institute, Translational Research Institute, Princess Alexandra Hospital, Brisbane, Australia.
Mills RA Mills Richard A RA Department of Ophthalmology, Flinders University, Adelaide, SA, Australia.
Craig JE Craig Jamie E JE Department of Ophthalmology, Flinders University, Adelaide, SA, Australia.
Klaver CC Klaver Caroline C W CC Department of Ophthalmology, Department of Epidemiology.
van Duijn CM van Duijn Cornelia M CM Department of Epidemiology.
Burdon KP Burdon Kathryn P KP Menzies Institute for Medical Research.
MacGregor S MacGregor Stuart S Statistical Genetics, QIMR Berghofer Medical Research Institute, Brisbane, Australia, stuart.macgregor@qimrberghofer.edu.au.
Mackey DA Mackey David A DA Centre for Ophthalmology and Visual Science, Lions Eye Institute, University of Western Australia.
INVESTIGATORS
JOURNAL
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
MEDLINE JOURNAL
MEDLINETA: Hum Mol Genet
COUNTRY: England
ISSNLINKING: 0964-6906
NLMUNIQUEID: 9208958
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
Research Support, Non-U.S. Gov't
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