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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

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Lucas, SEM, Zhou, T, Blackburn, NB, Mills, RA, Ellis, J, Leo, P, Souzeau, E, Ridge, B, Charlesworth, JC ORCID: 0000-0001-6201-3518, Lindsay, R, Craig, JE and Burdon, KP ORCID: 0000-0001-8217-1249 2018 , 'Rare, potentially pathogenic variants in 21 keratoconus candidate genes are not enriched in cases in a large Australian cohort of European descent' , PLoS One, vol. 13, no. 6 , pp. 1-15 , doi: 10.1371/journal.pone.0199178.

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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 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 Type: Article
Authors/Creators:Lucas, SEM 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
Keywords: cornea, targeted sequencing
Journal or Publication Title: PLoS One
Publisher: Public Library of Science
ISSN: 1932-6203
DOI / ID Number: 10.1371/journal.pone.0199178
Copyright Information:

© 2018 The Authors. Licensed under Creative Commons Attribution 4.0 International (CC BY 4.0) https://creativecommons.org/licenses/by/4.0/

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