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WNT10A exonic variant increases the risk of keratoconus by decreasing corneal thickness


Cuellar-Partida, G and Springelkamp, H and Lucas, SE and Yazar, S and Hewitt, AW and Iglesias, AI and Montgomery, GW and Martin, NG and Pennell, CE and van Leeuwen, EM and Verhoeven, VJM and Hofman, A and Uitterlinden, AG and Ramdas, WD and Wolfs, RCW and Vingerling, JR and Brown, MA and Mills, RA and Craig, JE and Klaver, CCW and van Duijn, CM and Burdon, KP and MacGregor, S and Mackey, DA, WNT10A exonic variant increases the risk of keratoconus by decreasing corneal thickness, Human Molecular Genetics, 24, (17) pp. 5060-5068. ISSN 0964-6906 (2015) [Refereed Article]


Copyright Statement

Copyright 2015 The Author

DOI: doi:10.1093/hmg/ddv211


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 > 5%). However, these studies typically ignore the large set of exonic variants whose minor allele frequency 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 x 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 from 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 x 10-5).

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:Lucas, SE (Dr Sionne Lucas)
UTAS Author:Hewitt, AW (Professor Alex Hewitt)
UTAS Author:Burdon, KP (Professor Kathryn Burdon)
ID Code:101070
Year Published:2015
Web of Science® Times Cited:41
Deposited By:Menzies Institute for Medical Research
Deposited On:2015-06-09
Last Modified:2017-11-06
Downloads:95 View Download Statistics

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