The disease can start with blurry or fuzzy vision, or with the weird sense that straight edges—like doorframes or windowsills—actually curve. Eventually, it can lead to a total loss of sharp, central vision, leaving those affected legally blind. The disease, age-related macular degeneration (AMD), is a leading cause of blindness among the elderly worldwide, affecting more that 15 percent of people aged 65 and older, approximately 150 million people globally. More than 10 million Americans have AMD, more than those who suffer from cataracts and glaucoma combined, according to the American Macular Degeneration Foundation. While some treatments exist, there is currently no way to cure or prevent the disease.
Now, a sweeping study has identified 52 common and rare genetic variants distributed across 34 genomic regions—including 13 previously unknown—that play a role in AMD. The findings, published online in the December 21, 2015, issue of Nature Genetics, offer clues to the onset and progression of the disease that may eventually lead to better treatments or a cure. “We think of these variants as potential targets for new drug development, or biomarkers that could identify people who are at very high risk, so we could potentially intervene early, even before the disease becomes apparent,” says Lindsay A. Farrer, chief of the biomedical genetics section at Boston University School of Medicine (MED) and a co-leader of the study. “That’s the hope.”
The International AMD Genomics Consortium, a group of 26 research centers worldwide that includes MED, conducted the study which was funded by the National Institutes of Health (NIH) and the Edward N. and Della L. Thome Memorial Foundation. The study is notable for its breadth: scientists analyzed more than 24 million genetic variants across the genomes of more than 43,000 unrelated people of predominantly European ancestry. The large study size allowed the scientists to detect rare variants that may only affect a small number of people or may have subtle effects. The study is also significant for its focus on “functional” variants—the portions of genes that code for proteins and so are more likely to have a biological effect.
This type of large, genome-wide study, which only became possible in the last decade as computing power and genotyping technology advanced, helps scientists create new hypotheses about what causes a disease and how it might be treated. Genetic science advanced differently in the past, says Farrer: scientists looking for clues about macular degeneration would explore the obvious places, like genes that encode proteins already known or hypothesized to impact the eye. Using this older approach, Farrer’s lab was one of three that independently discovered the gene for complement factor H—which greatly increases the risk of getting AMD—over a decade ago. (That discovery was published in Science in 2005.) This new, “agnostic” approach allows scientists to cast a wider net, says Farrer.
“There are biological systems outside the eye that affect diseases within the eye,” says Farrer, citing the cardiovascular system as an example. “You can start to think—what do these genes do, how do they relate to each other, how might they fit together in a pathway.”
The next step, says Farrer, is for labs involved in biomarker and drug discovery to dig into the data, tease them apart, and hopefully find some answers about AMD. “Imagine a time when we can predict who will get this disease, and when, and what treatment will work for them,” says Farrer. “That’s the dream.”