Published online March 3 in Nature Genetics, their study, “Seven New Loci Associated with Age-Related Macular Degeneration,” provides new directions for biological, genetic and therapeutic studies of macular degeneration.
Margaret A. Pericak-Vance, Ph.D., director of the John P. Hussman Institute for Human Genomics, who serves on the senior executive committee for the International AMD Genetics Consortium, is a senior author on the paper. Other UM coauthors include William K. Scott, Ph.D., professor in the Dr. John T. Macdonald Foundation Department of Human Genetics, and Stephen Schwartz, M.D., associate professor of ophthalmology, and Jaclyn L. Kovach, M.D., assistant professor of ophthalmology, at Bascom Palmer Eye Institute.
This research was conducted by the AMD gene consortium, which the NIH’s National Eye Institute created in 2010 to identify the remaining genetic risk variants for AMD. It is composed of more than 60 institutions, including UM, from around the globe.
“We hope that identifying seven new genes associated with macular degeneration will eventually lead to new therapies for this devastating disease, which robs people of their vision,” said Pericak-Vance, who has been researching the genetics of eye diseases for decades. In 2005, she and Scott were part of the team that identified genetic variation in complement factor H (CFH) as the first major genetic risk factor for age-related macular degeneration. The paper continues to be one of the most cited in biomedical research.
To accelerate understanding of AMD biology and help design new therapies, the researchers conducted a collaborative genome-wide association study of more than 17,100 people with advanced AMD, and more than 60,000 controls of European and Asian ancestry. Seven novel loci located near the genes COL8A1/FILIP1L, IER3/DDR1, SLC16A8, TGFBR1, RAD51B, ADAMTS9/MIR548A2, and B3GALTL were identified in this study.
The large collaborative effort allowed for the discovery of new smaller effect but genome-wide significant risk alleles. Some loci contribute differently to disease risk depending on gender and ethnicity. These risk variants provide good risk prediction. The results further strengthen implications of complement system involvement in AMD etiology.
University of Miami