期刊
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
卷 54, 期 7, 页码 5132-5135出版社
ASSOC RESEARCH VISION OPHTHALMOLOGY INC
DOI: 10.1167/iovs.13-12377
关键词
keratoconus; cornea; genetics; genome-wide association study; meta-analysis
资金
- Australian National Health and Medical Research Council (NHMRC) [APP1031362]
- Ophthalmic Research Institute of Australia
- NHMRC
- Australian National Health & Medical Research Council (NHMRC), Canberra, Australia [974159, 211069, 302068, 529923]
- Australian NHMRC, Canberra Australia (NHMRC) [512423, 475604, 529912]
- Wellcome Trust, United Kingdom, as part of Wellcome Trust Case Control Consortium 2 [085475/B/08/Z, 085475/08/Z]
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 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. 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 x 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.
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