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Replication and meta-analysis of candidate loci identified variation at RAB3GAP1 associated with keratoconus.
- Source :
-
Investigative ophthalmology & visual science [Invest Ophthalmol Vis Sci] 2013 Jul 30; Vol. 54 (7), pp. 5132-5. Date of Electronic Publication: 2013 Jul 30. - Publication Year :
- 2013
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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.<br />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 meta-analysis of this study with the adjusted P values of the previously published GWAS was conducted using the method of Fisher to combine P values.<br />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.<br />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.
Details
- Language :
- English
- ISSN :
- 1552-5783
- Volume :
- 54
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Investigative ophthalmology & visual science
- Publication Type :
- Academic Journal
- Accession number :
- 23833071
- Full Text :
- https://doi.org/10.1167/iovs.13-12377