March 4, 2013  Print

An international group of researchers has discovered seven new regions of the human genome—called loci—associated with increased risk of age-related macular degeneration (AMD), a leading cause of blindness. The Centre for Eye Research Australia and Westmead Millennium Institute for Medical Research are the only Australian institutes to be included in the AMD Gene Consortium, a network of international investigators representing 18 research groups.

The findings are reported online today in the journal Nature Genetics. This study represents the most comprehensive genome-wide analysis of genetic variations associated with AMD to date.

“This compelling analysis by the AMD Gene Consortium demonstrates the enormous value of effective collaboration,” said US-based National Eye Institute Director Paul A. Sieving, M.D., Ph.D.

“Combining data from multiple studies, this international effort provides insight into the molecular basis of AMD, which will help researchers search for causes of the disease and will inform future development of new diagnostic and treatment strategies.”

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. As AMD progresses, tasks such as reading, driving, and recognising faces become more difficult and eventually impossible. Some kinds of AMD are treatable if detected early, but no cure exists. An estimated one in seven Australians over the age of 50 is affected by AMD.

Scientists have shown that age, diet, and smoking influence a person’s risk of developing AMD. Genetics also play a strong role. AMD often runs in families and is more common among certain ethnicities, such as Asians and people of European descent.

The AMD Gene Consortium combined data from 18 research groups to increase the power of prior analyses. The current analysis identified seven new loci near genes and confirmed 12 loci identified in previous studies. All of these loci are scattered throughout the genome on many different chromosomes.

The consortium’s analysis included data from more than 17,100 people with the most advanced and severe forms of AMD, which were compared to data from more than 60,000 people without AMD. The 19 loci that were found to be 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. 

“While these findings certainly reinforce the notion that there is an important immunological aspect to this disease, it also indicates that a range of other biological pathways are involved,” said Associate Professor Paul Baird, one of the co-authors of the paper from the Centre for Eye Research Australia.

“This will allow us to develop new treatments that can be used to tackle the disease from different angles with the ultimate aim of translating these findings into improved treatments for patients.”

As with other common diseases, such as type 2 diabetes, an individual person’s risk for getting AMD is likely determined not by one but many genes. Further comprehensive DNA analysis of the areas around the 19 loci identified by the AMD Gene Consortium could turn up undiscovered rare genetic variants with a disproportionately large effect on AMD risk.

Discovery of such genes could greatly advance scientists’ understanding of AMD pathogenesis and their quest for more effective treatments.