Zhou, T and Souzeau, E and Sharma, S and Siggs, OM and Goldberg, I and Healey, PR and Graham, S and Hewitt, AW and Mackey, DA and Casson, RJ and Landers, J and Mills, R and Ellis, J and Leo, P and Brown, MA and MacGregor, S and Burdon, KP and Craig, JE, Rare variants in optic disc area gene CARD10 enriched in primary open-angle glaucoma, Molecular Genetics & Genomic Medicine, 4, (6) pp. 624-633. ISSN 2324-9269 (2016) [Refereed Article]
Copyright 2016 The Authors. Licensed under Creative Commons Attribution 4.0 International (CC BY 4.0) https://creativecommons.org/licenses/by/4.0/
METHODS: Participants fulfilled strict inclusion criteria of advanced POAG at a young age of diagnosis. Myocilin mutation carriers were excluded using direct sequencing. Whole exome sequencing was performed on 187 glaucoma cases and 103 local screened nonglaucoma controls then joint-called with exomes of 993 previously sequenced Australian controls. GWAS-associated genes were assessed for enrichment of rare predicted pathogenic variants in POAG. Significantly enriched genes were compared against Exome Aggregation Consortium (ExAC) public control.
RESULTS: Eighty-six GWAS disease or trait-associated glaucoma genes were captured and sequenced. CARD10 showed enrichment after Bonferroni correction for rare variants in glaucoma cases (OR = 13.2, P = 6.94 × 10-5) with mutations identified in 4.28% of our POAG cohort compared to 0.27% in controls. CARD10 was significantly associated with optic disc parameters in previous GWAS. The whole GWAS gene set showed no enrichment in POAG overall (OR = 1.12, P = 0.51).
CONCLUSION: We report here an enrichment of rare predicted pathogenic coding variants within a GWAS-associated locus in POAG (CARD10). These findings indicate that both common and rare pathogenic coding variants in CARD10 may contribute to POAG pathogenesis.
|Item Type:||Refereed Article|
|Keywords:||CARD10, genome‐wide association study, rare variants, whole exome sequencing|
|Research Division:||Medical and Health Sciences|
|Research Group:||Ophthalmology and Optometry|
|Objective Group:||Clinical Health (Organs, Diseases and Abnormal Conditions)|
|Objective Field:||Hearing, Vision, Speech and Their Disorders|
|Author:||Hewitt, AW (Dr Alex Hewitt)|
|Author:||Burdon, KP (Associate Professor Kathryn Burdon)|
|Deposited By:||Menzies Institute for Medical Research|
|Downloads:||24 View Download Statistics|
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