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Global network locates additional genes

The Macular Degeneration Center at Casey Eye Institute participated in a large international study that significantly expanded the number of genetic factors known to play a role in age-related macular degeneration (AMD).

The center was one of 26 research sites worldwide conducting the study of about 43,000 people as part of the International AMD Genomics Consortium. The findings may help improve our understanding of the biological causes that influence AMD and lead to more effective, targeted treatments. The study was published in December in the online journal Nature Genetics and was supported by the National Eye Institute, part of the National Institutes of Health.

“This is the largest study of its kind investigating AMD, and its findings represent a significant advance in our understanding of the genetic basis of the disease,” said Michael L. Klein, M.D., Casey’s lead investigator of the study and co-director of the Macular Degeneration Center. “By uncovering the biological mechanisms that drive AMD, we can develop more effective, targeted methods of prevention and treatment,” he says.

Other authors in the group from Casey were Tammy Martin, Ph.D., associate professor of ophthalmology and collaborators Matthew Johnson, Ph.D., and John Blangero, Ph.D., from the University of Texas at Rio Grande Valley.

AMD is a progressive disease that can damage central vision. A combination of genetic, environmental and lifestyle risk factors, such as smoking, influence the risk of advanced AMD, says Dr. Klein. Currently, there are no clinically approved treatments for the more common form of advanced AMD, called geographic atrophy or “dry” AMD. Although treatments are available for the other advanced form, neovascular or “wet” AMD, therapies do not cure the condition, nor work for everyone.

The consortium collected and analyzed genetic information from 43,566 people to systematically identify common and rare variations in genetic coding—called variants—associated with AMD. About half of the patients in the study had macular degeneration and about half did not.

“Because this study involved such a large population of AMD patients and controls, we were able to locate a number of new sites in the genome that may be connected to the disease,” says Dr. Klein.

As a result of the study’s findings, there are now 52 genetic variants associated with AMD. These variants are located among 34 regions of the genome; 16 of which had not been previously linked to AMD.

“The investigation is akin to looking at a Google map of the United States and attempting to pinpoint several leaders and satellite operations in a crime syndicate,” said a co-leader of the study, Anand Swaroop, Ph.D., chief of NEI’s Neurobiology-Neurodegeneration and Repair Laboratory. “It’s possible to find the key players by zooming in and seeing specific regions in rich detail, but first you have to know where to look. Pooling the genetic information from such a large population is what allowed us to look across the genome for possible culprits in AMD, even very small, very rare ones.”

For the first time the researchers also identified a variant linked to the wet (neovascular) form of AMD, which may point to reasons why therapy for this form of AMD is effective for some people but not everyone.

“Even with the pooling of genetic information from such a large population, the variants identified by the international consortium still cannot account for all of the heritability of AMD,” said Grace L. Shen, Ph.D., a group leader and director of the retinal diseases program at NEI. “We are, however, on track for discovering important variant genes that may play a role in AMD heritability.”

Read about the study in the Portland Business Journal

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