Seven Genetic Risk Factors Found to be Associated with Common Eye Disorder

A close-up crop of an eye surrounded by wrinkles. Image credit: National Eye Institute, National Institutes of Health

ANN ARBOR–(ENEWSPF)–March 4, 2013. The discovery of seven new regions of the human genome associated with macular degeneration could help scientists better understand who reaches the most severe stages of the disorder, says a University of Michigan researcher.

Gonçalo Abecasis, the Felix Moore Collegiate Professor of Biostatistics at the University of Michigan School of Public Health, is one member of an international group of researchers to make the latest discovery of loci associated with increased risk of age-related macular degeneration, a leading cause of blindness. The AMD Gene Consortium, a network of international investigators representing 18 research groups, also confirmed 12 loci identified in previous studies.

“Among the 12 previously known regions, the ones that have been examined in depth appear to predict onset of early stages of disease. We hope the new regions will help us predict a little better who’s going to get the most severe forms of the disorder,” Abecasis said. “We now want to look at each of these regions in detail and pin down the very specific culprit.”

The findings are reported online today in the journal Nature Genetics.

“The current study broadens our understanding of disease biology and provides many new targets for intervention. It is exciting to think that detailed analysis of these candidates will lead to the development of new treatments for this debilitating disease,” says first author Lars Fritsche, who started work on the study while at the University of Regensburg and is now a postdoctoral research fellow at the U-M School of Public Health.

Supported by the National Eye Institute, a part of the National Institutes of Health, the study represents the most comprehensive genome-wide analysis of genetic variations associated with AMD. The consortium’s analysis included data from more than 17,000 people with the most advanced and severe forms of AMD, which were compared to data from more than 60,000 people without the disorder.

“This compelling analysis by the AMD Gene Consortium demonstrates the enormous value of effective collaboration,” said NEI Director Paul Sieving. “Combining data from multiple studies, this international effort provides insight into the molecular basis of AMD.”

AMD affects the macula, a region of the retina responsible for central vision. The retina is the layer of light-sensitive tissue in the back of the eye that houses rod and cone photoreceptor cells. It is what humans rely on for tasks that require sharp vision, such as reading, driving and recognizing faces. As it 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 the disorder.

“There are a lot of different parts that have to work together for your eyes to age gracefully,” Abecasis said. “Macular degeneration is one of the most common things to go wrong with your vision, yet it is somewhat of a puzzle. For instance, given it has such a strong genetic effect, does disease only start when you age? It’s a little peculiar.”

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.

As with the previously discovered 12 loci, the seven just found are scattered throughout the genome on many different chromosomes. All 19 loci 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.

“Like a map that identifies neighborhoods where the electricity has been knocked out by a storm, the AMD Gene Consortium’s study effectively tagged regions within the genome where researchers are most likely to find short circuits in DNA that cause AMD,” said Anand Swaroop, chief of the NEI Laboratory of Neurobiology and Neurodegeneration and Repair, and one of the consortium leaders.

“Once you are in the right neighborhood, going block to block or house to house to look for downed power lines goes much faster. Likewise, by limiting their search to the 19 genomic regions identified by the AMD Gene Consortium, scientists can more efficiently search for specific genes and causative changes that play a role in AMD.”

Other lead authors included Lindsay A. Farrer, Boston University, Iris Heid, University of Regensburg, Germany, and Jonathan L. Haines, Vanderbilt University. An additional first author was Wei Chen, who was an SPH post-doctoral student during the study and now is at Children’s Hospital of Pittsburgh.

These studies were made possible by tools developed through the Human Genome Project and International HapMap Project.

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Adapted from a National Eye Institute Release