Primary angle closure glaucoma (PACG) is one of the major causes of blindness worldwide. The underlyinggenetic aetiology is complex in nature and molecular mechanism remains elusive. Here, we identify genomicalterations using haplotype-based genome-wide association study in 148 PACG and 92 anatomically predisposednon-glaucomatous individuals. Logistic regression was performed on each common haplotype (withinblocks of 3–8 SNPs) across the genotype and a total of 59 SNPs were found below genome wide suggestivethreshold (p\1e-05). We found majority of these SNPs (n = 13) are located in CNTNAP5 genic region. Theprioritized rs780010 of CNTNAP5 is also significantly associated with Cup to Disc ratio, which is a clinicalparameter directly correlated with glaucomatous neurodegeneration. We further validated rs780010, present inall the significant haplotype blocks with p-value = 2.131e-06 (discovery phase), in a separate replicationcohort (PACG, n = 50; control, n = 39) and observed significant association (p = 0.012, per G allele OR =2.3079; 95% CI: 1.23–4.33). Bioinformatics analyses also suggested neuronal expression of CNTNAP5 withactive chromatin structure. KEGG pathway analysis indicates towards pathways related to apoptosis andneurodegeneration. Overall, these results not only indicate a strong genetic association of CNTNAP5 locus withPACG but also suggest its potential involvement in glaucomatous neurodegeneration.
Volume 46, 2021
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