International Consortium Discovers New Genomic Regions Linked to Macular Degeneration.
An international group of researchers has discovered seven new regions of the human genome—called loci—that are associated with an increased risk of age-related macular degeneration (AMD), a leading cause of blindness.
Lindsay FarrerThe AMD Gene Consortium, a network of international investigators representing 18 research groups, also confirmed 12 loci identified in previous studies. The study, which is published online in Nature Genetics and represents the most comprehensive genome-wide analysis of variations associated with AMD, was co-authored by Lindsay A. Farrer, a professor and chief of the biomedical genetics section at the BU School of Medicine, and a professor of biostatistics and epidemiology at the School of Public Health. The study was funded by the National Eye Institute (NEI), a part of the National Institutes of Health.
“This compelling analysis by the AMD Gene Consortium demonstrates the enormous value of effective collaboration,” said NEI’s director, Dr. Paul A. Sieving. “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.”
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 the International HapMap Project, which identified common patterns of genetic variation within the human genome.
The AMD Gene Consortium combined data from 18 research groups to increase the power of prior analyses. The current analysis identified seven new loci near genes. As with the previously discovered 12 loci, these seven are scattered throughout the genome on many different chromosomes.
“Genetic research allows us to piece together disease pathways that may have their starting point much earlier in life,” said Farrer. “These newly identified genes, individually and collectively, provide novel clues and targets to evaluate for their potential therapeutic benefits.”
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 advance scientists’ understanding of AMD pathogenesis and the quest for more effective treatments.
AMD affects the macula, a region of the retina responsible for central vision. Compared with the rest of the retina, the macula is especially dense with cone photoreceptors and is what humans rely on 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 if detected early, but no cure exists. An estimated 2 million Americans have AMD.
Scientists have shown that age, diet, and smoking influence a person’s risk of developing AMD. Genetics also plays a strong role. AMD often runs in families and is more common among certain ethnicities, such as Asians and people of European descent.
For more information about AMD, visit http://www.nei.nih.gov/health/maculardegen/index.asp.
Submitted by: Lisa Chedekel
chedekel@bu.edu