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

Cuellar-Partida, Gabriel, Springelkamp, Henriet, Lucas, Sionne E. M., Yazar, Seyhan, Hewitt, Alex W., Iglesias, Adriana I., Montgomery, Grant W., Martin, Nicholas G., Pennell, Craig E., van Leeuwen, Elisabeth M., Verhoeven, Virginie J. M., Hofman, Albert, Uitterlinden, Andre G., Ramdas, Wishal D., Wolfs, Roger. C. W., Vingerling, Johannes R., Brown, Matthew A., Mills, Richard A., Craig, Jamie E., Klaver, Caroline C. W., van Duijn, Cornelia M., Burdon, Kathryn P., MacGregor, Stuart and Mackey, David A. (2015) WNT10A exonic variant increases the risk of keratoconus by decreasing corneal thickness. Human Molecular Genetics, 24 17: 5060-5068. doi:10.1093/hmg/ddv211

Author Cuellar-Partida, Gabriel
Springelkamp, Henriet
Lucas, Sionne E. M.
Yazar, Seyhan
Hewitt, Alex W.
Iglesias, Adriana I.
Montgomery, Grant W.
Martin, Nicholas G.
Pennell, Craig E.
van Leeuwen, Elisabeth M.
Verhoeven, Virginie J. M.
Hofman, Albert
Uitterlinden, Andre G.
Ramdas, Wishal D.
Wolfs, Roger. C. W.
Vingerling, Johannes R.
Brown, Matthew A.
Mills, Richard A.
Craig, Jamie E.
Klaver, Caroline C. W.
van Duijn, Cornelia M.
Burdon, Kathryn P.
MacGregor, Stuart
Mackey, David A.
Title WNT10A exonic variant increases the risk of keratoconus by decreasing corneal thickness
Journal name Human Molecular Genetics   Check publisher's open access policy
ISSN 1460-2083
Publication date 2015-06-05
Year available 2015
Sub-type Article (original research)
DOI 10.1093/hmg/ddv211
Open Access Status Not Open Access
Volume 24
Issue 17
Start page 5060
End page 5068
Total pages 9
Place of publication Oxford, United Kingdom
Publisher Oxford University Press
Collection year 2016
Language eng
Formatted 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).
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2016 Collection
UQ Diamantina Institute Publications
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