New England Eye Center, Tufts Medical Center Researchers and Collaborators Around the World Find Two New Genetic Clues to Development of Macular Degeneration


BOSTON, MA (Wednesday, August 31, 2011)– New England Eye Center (NEEC) the Ophthalmology Department at Tufts Medical Center and the principle ophthalmic teaching service for Tufts University School of Medicine is pleased to announce that researchers and collaborators from around the world have found two new genetic variants that influence the risk of developing advanced age-related macular degeneration, one of the leading causes of irreversible blindness in elderly individuals. The variants were identified in the largest meta-analysis of genome-wide association studies ever conducted for the disease, which is published on-line in the journal Human Molecular Genetics.

In the paper, “Common Variants near FRK/COL10A1 and VEGFA are associated with advanced age-related macular degeneration,” researchers found the variants in a pathway related to the formation of new blood vessels and in another pathway related to a type of collagen found in the part of the eye where macular degeneration develops.

“This study is a two year multi-center collaborative effort and has identified two new pathways for the development of macular degeneration,”said Johanna M. Seddon, MD, ScM, Director of the Ophthalmic Epidemiology and Genetics Service at New England Eye Center and Professor of Ophthalmology at Tufts University School of Medicine. “This expands our knowledge of the mechanisms underlying the disease and it may lead to new therapies based on these genetic pathways.”

The two new variants add to the risk prediction models the researchers developed in order to help identify people with a high risk of developing advanced macular degeneration.

About 7 percent of people over the age of 75 experience vision loss due to advanced macular degeneration. Macular degeneration occurs when cells in the macula, the part of the retina responsible for central vision, gradually die. This study included samples from people with advanced forms of both the faster progressing “wet” version of the disease and the slower developing “dry” type. Wet macular degeneration is caused by leaking blood vessels under the macula. Advanced dry macular degeneration is caused by a more gradual break down of cells in the macula which results in atrophy or loss of the normal functioning tissue in the center of the retina.

To find the two new variants, researchers first looked at more than 6 million single-nucleotide polymorphisms, or SNP’s, which are simply a single variation in just one of the four nucleotides that are strung together to form the DNA that makes up our genes. They performed a statistical analysis of these SNP’s using samples from 2,594 people with advanced macular degeneration and 4,134 people without it to identify potential candidate SNP’s related to the disease and found several “top hits”. Then to replicate the findings they added data from 10 research centers around the world to expand the sample size to 5,640 cases and 52,174 controls. This was the largest sample size for a genetic association study of advanced macular degeneration done to date. It allowed researchers to find associations with genome-wide significance, a generally-accepted threshold for genetic association studies that indicates their findings are unlikely to be due to chance.

Researchers discovered two novel SNP’s related to advanced macular degeneration, confirmed 10 previously known or suspected associations and identified other potential new SNP’s. One of the new confirmed SNP’s is near the VEGFA gene, which is involved with angiogenesis, the formation of new blood vessels. VEGFA is a target of several treatments for wet macular degeneration, including the drug ranibizumab. The SNP identified by this analysis is a new variant and is unrelated to candidate SNP’s previously reported. In this new study, AMD was found to be significantly related to only the new variant near VEGFA and not the other SNPs.

The other new SNP is near the FRK/COLA10A1 gene, which encodes for a type of collagen found in the extracellular matrix, the lattice of proteins that makes up a layer underneath the retina and is involved in AMD. This is particularly interesting because the investigators reported in the journal PNAS in 2010 that another gene called COL8A1 in the collagen pathway was related to AMD, and this same gene is also suggested in the current study.

Collaborators included Mark Daly PhD, and other investigators from Massachusetts General Hospital and Broad Institute in Boston, John Ioannidis, MD from Tufts Medical Center and Stanford University, as well as collaborators from Genentech, Duke University, Johns Hopkins University, Columbia University, DeCode in Iceland, Creteil in France, Washington University in Missouri, Belfast in Ireland, and Melbourne in Australia.


About Johanna M. Seddon, M.D. ScM

Johanna M. Seddon, M.D., ScM, is an Ophthalmologist and leading researcher at New England Eye Center at Tufts Medical Center. Dr. Seddon is a pioneer in nutritional research in age-related macular degeneration and cataract, as well as in the field of ophthalmic epidemiology and genetics. For more than 20 years, Dr. Seddon has received NIH grants on epidemiologic, biologic, and genetic biomarkers for macular degeneration, and has made original contributions in these areas.

She was a vice-president and trustee of ARVO, currently holds a gold ARVO fellow status and is the recipient of the inaugural Maurice F. Rabb, Jr. Award from Prevent Blindness America, for dedication and contributions to prevention and treatment of age-related macular degeneration.


About New England Eye Center

New England Eye Center (NEEC) is the ophthalmology department for Tufts Medical Center and Tufts University School of Medicine. New England Eye Center offers a full range of comprehensive ophthalmology including treatments for cataracts, glaucoma, macular degeneration, pediatric ophthalmology and aesthetic surgery. New England Eye Center is also a leading provider of Laser Vision Correction in Greater Boston and New England offering a full range of vision correction procedures for all types of eye conditions. For more information about the New England Eye Center, go to


About Tufts Medical Center

TuftsMedical Center is an exceptional, not-for-profit, 415-bed academic medical center that is home to both a full-service hospital for adults and Floating Hospital for Children. Conveniently located in downtown Boston, the Medical Center is the principal teaching hospital for Tufts University School of Medicine. New England Eye Center (NEEC) is the ophthalmology department for Tufts Medical Center and Tufts University School of Medicine. New England Eye Center offers a full range of comprehensive ophthalmology including treatments for cataracts, glaucoma, macular degeneration, pediatric ophthalmology and aesthetic surgery. For more information, please visit


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