Format

Send to

Choose Destination
Hum Mol Genet. 2015 Sep 1;24(17):5060-8. doi: 10.1093/hmg/ddv211. Epub 2015 Jun 5.

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

Author information

1
Statistical Genetics, QIMR Berghofer Medical Research Institute, Brisbane, Australia.
2
Department of Ophthalmology, Department of Epidemiology.
3
Menzies Institute for Medical Research.
4
Centre for Ophthalmology and Visual Science, Lions Eye Institute, University of Western Australia.
5
School of Medicine, Menzies Research Institute Tasmania, University of Tasmania, Hobart, Australia, Centre for Eye Research Australia, Melbourne University, Melbourne, Australia.
6
Molecular Epidemiology.
7
Genetic Epidemiology, QIMR Berghofer Medical Research Institute, Brisbane, Australia and.
8
School of Women's and Infants' Health, University of Western Australia, Perth, Australia.
9
Department of Epidemiology.
10
Department of Epidemiology, Netherlands Consortium for Healthy Ageing, Netherlands Genomics Initiative, the Hague 2593 CE, The Netherlands.
11
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.
12
Department of Ophthalmology.
13
University of Queensland Diamantina Institute, Translational Research Institute, Princess Alexandra Hospital, Brisbane, Australia.
14
Department of Ophthalmology, Flinders University, Adelaide, SA, Australia.
15
Statistical Genetics, QIMR Berghofer Medical Research Institute, Brisbane, Australia, stuart.macgregor@qimrberghofer.edu.au.

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)).

PMID:
26049155
DOI:
10.1093/hmg/ddv211
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Silverchair Information Systems
Loading ...
Support Center