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dc.contributor.authorBae, Ha Ae
dc.contributor.authorMills, Richard Arthur
dc.contributor.authorLindsay, Richard
dc.contributor.authorPhillips, Tony
dc.contributor.authorMitchell, Paul
dc.contributor.authorWang, Jie Jin
dc.contributor.authorCoster, Douglas John
dc.contributor.authorCraig, Jamie E
dc.contributor.authorBurdon, Kathryn Penelope
dc.date.accessioned2014-02-27T01:35:27Z
dc.date.available2014-02-27T01:35:27Z
dc.date.issued2013-07-30
dc.identifier.citationBae, H. A., Mills, R. A., Lindsay, R. G., Phillips, T., Coster, D. J., Mitchell, P., Wang, J. J., Craig, J. E., Burdon, K. P. Replication and meta-analysis of candidate loci identified variation at RAB3GAP1 associated with keratoconus. Invest. Ophthalmol. Vis. Sci. 2013;54(7):5132-35en
dc.identifier.issn0146-0404
dc.identifier.urihttp://hdl.handle.net/2328/27479
dc.identifier.urihttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3729241/
dc.description.abstractKeratoconus 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.en
dc.description.sponsorshipSupported by a Project grant from the Australian National Health and Medical Research Council (NHMRC; APP1031362), the Ophthalmic Research Institute of Australia (for recruitment of this cohort), and a Career Development Award (KPB) and a Practitioner Fellowship (JEC) from the NHMRC. The Blue Mountains Eye Study (BMES) was supported by the Australian National Health & Medical Research Council (NHMRC), Canberra, Australia (Project Grants 974159, 211069, 302068, and Centre for Clinical Research Excellence Grant 529923). The BMES GWAS and genotyping costs were supported by Australian NHMRC, Canberra Australia (NHMRC Project Grants 512423, 475604, and 529912), and the Wellcome Trust, United Kingdom, as part of Wellcome Trust Case Control Consortium 2 (A Viswanathan, P McGuffin, P Mitchell, F Topouzis, P Foster, Grants 085475/B/08/Z and 085475/08/Z).en
dc.language.isoenen_US
dc.publisherAssociation for Research in Vision and Ophthalmology (ARVO)en
dc.relationhttp://purl.org/au-research/grants/nhmrc/1031362en
dc.rightsCopyright © Association for Research in Vision and Ophthalmology.en_US
dc.subjectcorneaen_US
dc.subjectgeneticsen_US
dc.subjectgenome-wide association studyen_US
dc.subjectkeratoconusen_US
dc.subjectmeta-analysisen_US
dc.titleReplication and meta-analysis of candidate loci identified variation at RAB3GAP1 associated with keratoconusen_US
dc.typeArticleen
dc.relation.grantnumberNHMRC/1031362en_US
dc.identifier.doihttps://doi.org/10.1167/iovs.13-12377en
dc.rights.holderAssociation for Research in Vision and Ophthalmology.en_US
local.contributor.authorOrcidLookupLindsay, Richard: http://orcid.org/0000-0002-2430-3861en_US


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