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To identify genetic loci associated with open angle glaucoma (OAG) blindness.

The researchers performed a genome-wide association study covering nearly 300,000 SNPs in 590 individuals with advanced OAG and 3,956 healthy controls of European descent. This was followed up with further genotyping in 892 cases and 4,582 controls from three replication cohorts, also of European descent, along with further lab-based functional work.

The initial discovery cohort linked two genomic regions on chromosomes 1q24 (near the TMCO1 gene) and 9p21 (in the CDKN2B-AS1 gene) with OAG at genome-wide significance. The top SNPs at these two locations also showed association at less stringent statistical significance levels in the replication cohorts. Functional studies showed that TMCO1 and CDKN2B-AS1 may play a role in glaucoma through retinal ganglion cell death.

Carriers of one or more risk allele at the two genes identified by the researchers in this study impart a three-fold increase in risk for advanced OAG. Identification of the CDKN2B-AS1 gene on chromosome 9p21, as well as increased expression of both CDKN2A and CDKN2B (also located on 9p21) in a rat glaucoma model, highlight the importance of this genomic region in the genetic risk of OAG.

Glaucoma can lead to complete blindness if left untreated but if caught early can be treated to slow down any further loss of sight. However, because OAG progresses very slowly patients often do not notice the loss of peripheral vision until the disease is advanced. If those at increased risk of developing OAG can be identified early, treatment can be given in a timely manner to minimize the loss of sight caused by OAG. The findings from this study could lead to improved risk prediction and even diagnosis, suggesting plausible biochemical pathways involved in OAG. More research is needed though to confirm exactly which genes are involved, as the authors themselves suggest that the ALDH9A1 gene rather than TMCO1 could be responsible for the observed association.