An A*STAR led team uncovered new genes associated with primary angle closure glaucoma.
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A detailed search of the human genome has revealed five genetic locations linked to a form of glaucoma which causes many cases of blindness in Asia. Led by A*STAR, the large international team was able to access enough data on genetic markers to provide insights into the cellular processes that allow the disease to progress.
Chiea-Chuen Khor from the A*STAR Genome Institute of Singapore and co-workers focused on primary angle closure glaucoma (PACG), a form of the disease that is more prevalent in Asians than in people of other ethnicities and that has not been studied to the same extent as primary open angle glaucoma (POAG). The team has previously helped to expose genes linked to exfoliation syndrome, a common cause of POAG, particularly in Northern Europe and America.
“The main challenge of the study was to accumulate enough PACG patients and controls to be credible,” says Khor. “We obtained such a large number of samples due to help from glaucoma surgeons, many of whom are close collaborators of our joint research leader, Professor Aung Tin from the Singapore National Eye Center.”
Overall, the team amassed samples from more than 10,000 PACG patients and almost 30,000 controls, from 15 countries in Asia, Europe and South America. They performed a genome-wide association study, searching the entire genome to find genetic variants associated with PACG.
“Because we were assessing more than a million individual genetic markers, we adopted a very stringent statistical threshold for declaring markers to be significantly related to the disease,” explains Khor. “The markers that surpassed the threshold were tested against other sample collections as a further ‘replication’ step, providing a very high degree of technical scrutiny for newly identified markers.”
The study identified five new genetic loci associated with PACG, which include sequences linked to cell-to-cell adhesion and the metabolism of the structural protein, collagen. Both these processes are vital for healthy eyes, Khor explains.
“Even a subtle change in the finely balanced physiology of cell-cell adhesion and collagen metabolism in a space as small and tight as the anterior eye chamber could lead to cellular abnormalities, changing anatomical angles and triggering the development of glaucoma,” Khor says.
The researchers aim to study the roles of the genes they identified in more detail, using PACG disease models such as mice and, eventually, human eye tissues.
“Our plan is to definitively identify the pathological genes for PACG before attempting biological investigations on scarce and valuable human tissues,” says Khor.
The A*STAR-affiliated researchers contributing to this research are from the Genome Institute of Singapore.
