A professor from Case Western Reserve University School of Medicine is one of the lead authors of a study identifying seven new regions of the human genome that are associated with increased risk of age-related macular degeneration (AMD), a leading cause of blindness among older adults.
The AMD Gene Consortium, a network of international investigators representing 18 research groups, also confirmed the existence of 12 other regions—called loci—that had been identified in previous studies. The authors report their findings online in the journal Nature Genetics. Supported by the National Eye Institute (NEI), a part of the National Institutes of Health, the study represents the most comprehensive genome-wide analysis of genetic variations associated with AMD.
“This work represents a big step forward toward solving why some people get AMD, while others do not,” said Sudha Iyengar, professor of epidemiology and biostatistics at Case Western Reserve School of Medicine and a member of the consortium’s senior executive committee. “This disease is not caused by a single change in the DNA, but represents many events that accumulate over the lifetime of a patient. Identification of these genes provides molecular windows into the AMD disease process.”
AMD affects the macula, a region of the retina responsible for central vision. The retina is the layer of light-sensitive tissue in the back of the eye that houses rod and cone photoreceptor cells. Compared with the rest of the retina, the macula is especially dense with cone photoreceptors; humans rely on the macula for tasks that require sharp vision, such as reading, driving, and recognizing faces. As AMD progresses, such tasks become more difficult and eventually impossible. Some kinds of AMD are treatable, but no cure exists. An estimated 2 million Americans suffer from AMD.
Since the 2005 discovery that certain variations in the gene for complement factor H—a component of the immune system—are associated with major risk for AMD, research groups around the world have conducted genome-wide association studies to identify other loci that affect AMD risk. These studies were made possible by tools developed through the Human Genome Project, which mapped human genes, and related projects, such as the International HapMap Project, which identified common patterns of genetic variation within the human genome.
The consortium’s analysis included data from more than 17,100 people with the most advanced and severe forms of AMD, which were compared to data from more than 60,000 people without AMD. The 19 loci that were found to be associated with AMD implicate a variety of biological functions, including regulation of the immune system, maintenance of cellular structure, growth and permeability of blood vessels, lipid metabolism, and atherosclerosis.
As with other common diseases, such as Type 2 diabetes, an individual person’s risk for getting AMD is likely determined not by one but many genes. Further comprehensive DNA analysis of the areas around the 19 loci identified by the AMD Gene Consortium could turn up undiscovered rare genetic variants with a disproportionately large effect on AMD risk. Discovery of such genes could greatly advance scientists’ understanding of AMD pathogenesis and their quest for more effective treatments.
“This compelling analysis by the AMD Gene Consortium demonstrates the enormous value of effective collaboration,” said NEI director Paul A. Sieving, MD, PhD. “Combining data from multiple studies, this international effort provides insight into the molecular basis of AMD, which will help researchers search for causes of the disease and will inform future development of new diagnostic and treatment strategies.”
Other lead authors of the study include: Gonçalo R. Abecasis, University of Michigan; Lindsay A. Farrer, Boston University; Iris Heid, University of Regensburg, Germany; and Jonathan L. Haines, Vanderbilt University.
For more information about AMD, visit nei.nih.gov/health/
This research was supported in part by the NEI Intramural Research Program and NIH grants Z01EY000475, U10EY006594, R01EY015810, R01EY015286, R03EY013438, R01EY010605, R24EY017404, R01EY014458, R01EY017362, R24EY017404, R01EY013834, K23EY000365, R01EY009611, R01EY021532, R01EY021163, R01EY013435, R24EY019861, P30EY019007, T32EY021453, R01EY012118, R01EY022005, R01EY016862, R01EY014467, K12EY16335, R01EY11309, R01EY09859, R01EY014428, R01EY018660, R01EY019270, U54HG006542, P01CA87969, R01CA49449, and R01HL35464.