Dataset Information

Replication and meta-analysis of candidate loci identified variation at RAB3GAP1 associated with keratoconus.

ABSTRACT: 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.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.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.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.

SUBMITTER: Bae HA

PROVIDER: S-EPMC3729241 | biostudies-literature | 2013 Jul

REPOSITORIES: biostudies-literature

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Replication and meta-analysis of candidate loci identified variation at RAB3GAP1 associated with keratoconus.

Bae Ha Ae HA Mills Richard A D RA Lindsay Richard G RG Phillips Tony T Coster Douglas J DJ Mitchell Paul P Wang Jie Jin JJ Craig Jamie E JE Burdon Kathryn P KP

Investigative ophthalmology & visual science 20130730 7

<h4>Purpose</h4>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.<h4>Methods</h4>We geno ...[more]

PMID: 23833071

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Dataset Information

Replication and meta-analysis of candidate loci identified variation at RAB3GAP1 associated with keratoconus.

Publications

Replication and meta-analysis of candidate loci identified variation at RAB3GAP1 associated with keratoconus.

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