Genes clarify risks for macular degeneration

BOSTON U. (US) — Genetic research is narrowing the genetic influences that affect a person’s risk of developing age-related macular degeneration.

The AMD Gene Consortium, a network of international investigators representing 18 research groups, has discovered seven new regions of the human genome—called loci—that are associated with increased risk of age-related macular degeneration (AMD), a leading cause of blindness. The team also confirmed 12 loci identified in previous studies.

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.


Compared with the rest of the retina, the macula is especially dense with cone photoreceptors and is what humans rely on for tasks that require sharp vision, such as reading, driving and recognizing faces.

As the condition progresses, such tasks become more difficult and eventually impossible. Some types of AMD are treatable if detected early, but no cure exists. An estimated 2 million Americans have AMD.

“Genetic research allows us to piece together disease pathways that may have their starting point much earlier in life,” says Lindsay A. Farrer, chief of the biomedical genetics section and professor at Boston University Schools of Medicine and Public Health.

“These newly identified genes, individually and collectively, provide novel clues and targets to evaluate for their potential therapeutic benefits.”

“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,” Says National Eye Institute (NEI) Director, Paul A. Sieving.

Since the 2005 discovery that certain variations in the gene for complement factor H—a component of the immune system—are associated with major risk for AMD, research groups have conducted genome-wide association studies to identify other loci that affect AMD risk.

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. As with the previously discovered 12 loci, these seven loci are scattered throughout the genome on many different chromosomes. The findings are published in Nature Genetics.

Untangling genetic risk factors

“A large number of samples was needed to detect additional genetic variants that have small but significant influences on a person’s disease risk,” says Hemin Chin, NEI associate director for ophthalmic genetics, who assembled the consortium and helped coordinate the study.

“By cataloging genetic variations associated with AMD, scientists are better equipped to target corresponding biological pathways and study how they might interact and change with age or other factors, such as smoking.”

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 found 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.

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 team 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.

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.

AMD typically presents later in life, but identifying genetic variants associated with the disease, all of which are present at birth, could help future studies determine how to stop the disease from progressing and even from occurring.

Researchers from the University of Michigan, the University of Regensburg, and Vanderbilt University contributed to the study.

The National Eye Institute, a part of the National Institutes of Health, and the Edward N. & Della L. Thome Memorial Foundation supported the research.

Source: Boston University