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Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease
Published on: April 4, 2018
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Analysis of variants in Chinese individuals with primary open-angle glaucoma using molecular inversion probe
Ting Liu1, Chao Tang2, Xiaolong Shi2
1Department of ophthalmology, Daping Hospital of the Army Medical University, Chongqing, China.
Molecular Vision
|June 2, 2020
Summary
Rare coding variants in genes associated with primary open-angle glaucoma (POAG) are enriched in Chinese patients. These potentially disease-relevant variants may contribute to POAG risk and early disease onset.
Area of Science:
- Ophthalmology
- Genetics
- Molecular Biology
Background:
- Genome-wide association studies (GWASs) and genetic linkage analyses have identified numerous genomic loci linked to primary open-angle glaucoma (POAG).
- While causative genes for POAG have been studied, investigations into coding region variants within GWAS-identified genes remain limited.
- Further research is crucial to determine if these genes harbor rare coding variants that contribute to POAG pathogenesis.
Purpose of the Study:
- To identify potentially disease-relevant variants (PDVs) in POAG-associated genes within a Chinese cohort.
- To investigate the role of rare coding variants in POAG etiology using molecular inversion probe (MIP)-based panel sequencing.
Main Methods:
- Sequencing of 26 candidate genes using MIP-based panel sequencing.
- Analysis of 235 patients with POAG and 241 control subjects from Chinese population.
- Statistical comparison of PDV prevalence between POAG patients and controls.
Main Results:
- 82 PDVs were identified in 66 POAG patients, compared to 18 PDVs in 19 controls, showing significant enrichment in the POAG cohort (28.1% vs. 7.9%, p = 8.629e-09).
- Five genes (ATXN2, TXNRD2, MYOC, FOXC1, CDKN2B) exhibited a statistically significant difference in PDV prevalence between cases and controls.
- A novel stop-loss mutation in EFEMP1 (p.Ter494Glu) was identified in two sisters with POAG, suggesting it as a potential disease-causing mutation. PDVs were associated with earlier age at diagnosis.
Conclusions:
- Rare coding variants in POAG-associated genes likely contribute to POAG risk.
- These variants may have functional effects that modify POAG susceptibility.
- The findings highlight the importance of investigating rare coding variants in understanding POAG genetics.
