Dataset Information

Rare variants in optic disc area gene CARD10 enriched in primary open-angle glaucoma.

ABSTRACT:

Background

Genome-wide association studies (GWAS) have identified association of common alleles with primary open-angle glaucoma (POAG) and its quantitative endophenotypes near numerous genes. This study aims to determine whether rare pathogenic variants in these disease-associated genes contribute to POAG.

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.

SUBMITTER: Zhou T

PROVIDER: S-EPMC5118207 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

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Publications

Rare variants in optic disc area gene <i>CARD10</i> enriched in primary open-angle glaucoma.

Zhou Tiger T Souzeau Emmanuelle E Sharma Shiwani S Siggs Owen M OM Goldberg Ivan I Healey Paul R PR Graham Stuart S Hewitt Alex W AW Mackey David A DA Casson Robert J RJ Landers John J Mills Richard R Ellis Jonathan J Leo Paul P Brown Matthew A MA MacGregor Stuart S Burdon Kathryn P KP Craig Jamie E JE

Molecular genetics & genomic medicine 20161003 6

<h4>Background</h4>Genome-wide association studies (GWAS) have identified association of common alleles with primary open-angle glaucoma (POAG) and its quantitative endophenotypes near numerous genes. This study aims to determine whether rare pathogenic variants in these disease-associated genes contribute to POAG.<h4>Methods</h4>Participants fulfilled strict inclusion criteria of advanced POAG at a young age of diagnosis. Myocilin mutation carriers were excluded using direct sequencing. Whole e ...[more]

PMID: 27896285

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