Supported by the National Eye Institute (NEI), part of the National Institutes of Health (NIH), the findings may help improve our understanding of the biological processes that lead to AMD and identify new therapeutic targets for potential drug development and predictive genetic tests. The results are published in today’s issue of the journal Nature Genetics. “It was exciting to be part of this high-quality international consortium, representing an important step forward in international research collaboration,” said co-author Daniel Weeks, Ph.D., professor in the departments of Human Genetics and Biostatistics at Pitt Public Health. “This is a study that none of us could have done alone—we never could have achieved the statistical power needed to draw meaningful results. This work opens the doors to potential new treatments for a devastating disease.” AMD is a progressive disease that causes the death of the retinal photoreceptors, the light-sensitive cells at the back of the eye. The most severe damage occurs in the macula, a small area of the retina that is needed for sharp, central vision necessary for reading, driving and other daily tasks. There currently are no Food and Drug Administration-approved treatments for the more common form of advanced AMD, called geographic atrophy or “dry” AMD.
AMD is caused by a combination of genetic, environmental and lifestyle risk factors. For example, smoking increases the risk of the disease, while eating leafy greens and fish may reduce the risk. Up to this point, researchers had identified 21 regions of the genome—called loci—that influence the risk of AMD. The new research brings the number to 34 loci.
The International AMD Genomics Consortium, which includes 26 centers worldwide, collected and analyzed the genetic data from 43,566 people of predominantly European ancestry to systematically identify common and rare variations in genetic coding—called variants—associated with AMD. Pitt Public Health contributed data from 839 people recruited in the Pittsburgh region by former Pitt professor Michael Gorin, M.D., now with the University of California, Los Angeles.
As a result, the research team has discovered a total of 52 genetic variants that are associated with AMD, providing a foundation for further genetic studies of the disease. The next step is to investigate what the variants are doing to the genes and how they affect gene function—whether that be turning the genes on or off, interacting with other genes to spur a chain reaction leading to AMD, or some other action.
For the first time, the researchers also identified a variant specific to the neovascular, or “wet,” form of AMD, which may point to reasons why therapy for this form of the disease 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.”
The study was funded in part by the NEI Intramural Research Program and by NEI grants EY023164, EY012118, EY022310, T32-EY023194, P30-EY005722, EY0022005, EY016862 and EY022310. The study also was supported by NIH grants from the National Human Genome Research Institute (HG006513, HG007022, 1U01HG006389), the National Institute on Aging (AG019085), and the National Center for Advancing Translational Sciences (UL1TR000427).