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 Type:	Refereed Article
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:	28
Deposited By:	Menzies Institute for Medical Research
Deposited On:	2014-03-26
Last Modified:	2017-11-06
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