An international team of scientists that includes researchers from the University of Michigan has identified 16 new genetic variations for age-related macular degeneration.
Their findings nearly double the number of regions, or loci, associated with the disease.
The International AMD Genomics Consortium with its 26 participating institutions also confirmed several previously reported AMD risk genes in the study involving 43,000 people. With its large sample size and high density of genetic variants, the study was able to prioritize candidate variants within identified risk loci, which in turn will help to plan more efficient follow-up experiments.
Furthermore, the study detected an enrichment of very rare protein coding variants in AMD cases within three of the known AMD risk genes, CFH, CFI and TIMP3. With observed frequencies in controls below 0.1 percent and strong risk effects, these findings indicate that there exist very personal situations that noticeably can shift the risk of developing the disease.
The research brings to 52 the number of identified common and rare variants associated with the disease that causes vision loss in people 50 and older. Together, these could explain up to 60 percent of the inherited genetic risk for the disease.
The consortium’s findings are reported today in Nature Genetics.
The study’s lead author, Dr. Lars Fritsche, research investigator in the U-M School of Public Health Center for Statistical Genetics, said the large size of the sample along with advancements in genotyping technology allowed the study team to dissect the combined contributions of common and rare variants.
“Often, we have common variant associations and don’t know exactly why they are associated with disease, but with these rare variant associations we have observed protein coding changes that could have direct functional consequences,” said Dr. Fritsche, adding that the consortium’s finding of these rare variants at such low frequencies points to the need for even larger studies, and for genome sequencing rather than genotyping.
“Our results also emphasize that we need to continue to work together to have the statistical and analytical power to find interesting rare variants that can point us to the disease mechanism itself,” he said.
AMD is a neurodegenerative disease that is estimated to affect 30-50 million people globally, and growing. It involves a loss of sight in the center of the visual field, caused by damage to the retina. It comes in two forms, geographic atrophy or “dry” AMD, and neovascular “wet” AMD.
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