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Replication and meta-analysis of candidate loci identified variation at RAB3GAP1 associated with keratoconus
Citation
Bae, HA and Mills, RAD and Lindsay, RG and Phillips, T and Coster, DJ and Mitchell, P and Wang, JJ and Craig, JE and Burdon, KP, Replication and meta-analysis of candidate loci identified variation at RAB3GAP1 associated with keratoconus, Investigative Ophthalmology and Visual Science (Iovs), 54, (7) pp. 5132-5135. ISSN 0146-0404 (2013) [Refereed Article]
DOI: doi:10.1167/iovs.13-12377
Abstract
PURPOSE. Keratoconus is a common complex corneal ectasia that can lead to severe visual impairment. Although a genetic component is well recognized, the genetic risk factors for keratoconus are yet to be fully elucidated. A recent genome-wide association study (GWAS) by Li et al. identified 15 potentially associated single nucleotide polymorphisms (SNPs). Here, we aimed to replicate these associations, and conduct a meta-analysis of the current and previous studies. METHODS. We genotyped the 15 reported associated SNPs in 524 Australian Caucasian cases with keratoconus and 2761 controls. Association analysis was conducted in PLINK. A metaanalysis of this study with the adjusted P values of the previously published GWAS was conducted using the method of Fisher to combine P values. RESULTS. Our Australian cohort showed association (P < 0.003) at SNPs near RAB3GAP1, KCND3, IMMPL2, and in a gene desert on chromosome 13q33.3, providing evidence of replication of the published results. The meta-analysis showed SNP rs4954218 near RAB3GAP1 gene was associated significantly with keratoconus, with P &= 9.26 × 10-9 passing the genome-wide significance level. CONCLUSIONS. Although the mechanism of disease association is yet to be determined, SNP rs4954218 is associated consistently with keratoconus and likely tags a functional variant that contributes to disease susceptibility.
Item Details
Item Type: | Refereed Article |
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Keywords: | Cornea; Genetics; Genome-wide association study; Keratoconus; Meta-analysis |
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: | Burdon, KP (Professor Kathryn Burdon) |
ID Code: | 90067 |
Year Published: | 2013 |
Web of Science® Times Cited: | 29 |
Deposited By: | Menzies Institute for Medical Research |
Deposited On: | 2014-03-26 |
Last Modified: | 2017-11-06 |
Downloads: | 0 |
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