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Rare, potentially pathogenic variants in 21 keratoconus candidate genes are not enriched in cases in a large Australian cohort of European descent
Citation
Lucas, SE and Zhou, T and Blackburn, NB and Mills, RA and Ellis, J and Leo, P and Souzeau, E and Ridge, B and Charlesworth, JC and Lindsay, R and Craig, JE and Burdon, KP, Rare, potentially pathogenic variants in 21 keratoconus candidate genes are not enriched in cases in a large Australian cohort of European descent, PLoS One, 13, (6) Article e0199178. ISSN 1932-6203 (2018) [Refereed Article]
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Copyright Statement
© 2018 The Authors. Licensed under Creative Commons Attribution 4.0 International (CC BY 4.0) https://creativecommons.org/licenses/by/4.0/
DOI: doi:10.1371/journal.pone.0199178
Abstract
Many genes have been suggested as candidate genes for keratoconus based on their function, their proximity to associated polymorphisms or due to the identification of putative causative variants within the gene. However, very few of these genes have been assessed for rare variation in keratoconus more broadly. In contrast, VSX1 and SOD1 have been widely assessed, however, the vast majority of studies have been small and the findings conflicting. In a cohort of Australians of European descent, consisting of 385 keratoconus cases and 396 controls, we screened 21 keratoconus candidate genes: BANP, CAST, COL4A3, COL4A4, COL5A1, FOXO1, FNDC3B, HGF, IL1A, IL1B, ILRN, IMMP2L, MPDZ, NFIB, RAB3GAP1, RAD51, RXRA, SLC4A11, SOD1, TF and VSX1. The candidate genes were sequenced in these individuals by either whole exome sequencing or targeted gene sequencing. Variants were filtered to identify rare (minor allele frequency <1%), potentially pathogenic variants. A total of 164 such variants were identified across the two groups with no variants fulfilling these criteria in cases in IL1RN, BANP, IL1B, RAD51 or SOD1. The frequency of variants was compared between cases and controls using chi-square or Fishers' Exact tests for each gene with at least one rare potentially pathogenic variant identified in the case cohort. The number of rare potentially pathogenic variants per gene ranged from three (RXRA) to 102 (MPDZ), however for all genes, there was no difference in the frequency between the cases and controls. We conclude that rare potentially pathogenic variation in the 21 candidate genes assessed do not play a major role in keratoconus susceptibility and pathogenesis.
Item Details
| Item Type: | Refereed Article |
|---|---|
| Keywords: | cornea, targeted sequencing |
| 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: | Lucas, SE (Ms Sionne Lucas) |
| UTAS Author: | Blackburn, NB (Dr Nicholas Blackburn) |
| UTAS Author: | Charlesworth, JC (Dr Jac Charlesworth) |
| UTAS Author: | Burdon, KP (Professor Kathryn Burdon) |
| ID Code: | 126983 |
| Year Published: | 2018 |
| Funding Support: | National Health and Medical Research Council (1104700) |
| Web of Science® Times Cited: | 8 |
| Deposited By: | Menzies Institute for Medical Research |
| Deposited On: | 2018-07-06 |
| Last Modified: | 2019-02-25 |
| Downloads: | 68 View Download Statistics |
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