Genetic Risk Factors Found for Macular Degeneration

Seven new regions of the human genome have been found to be associated with an increased risk of age-related macular degeneration (AMD).

A leading cause of blindness, AMD, often runs in families and is more common among certain ethnicities, such as people of Asian or European descent.

The AMD Gene Consortium, a network of international investigators, that was established by the US National Eye Institute (Bethesda, MD, USA), 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 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.

Using ribonucleic acid (RNA) sequencing, the teams examined the mRNA levels of 85 genes within 100 kilo bases (kb) of their index single nucleotide polymorphisms (SNPs) in postmortem human retina. Two genes showed differential expression in the postmortem retina of young, whose age range was 17 to 35 years and elderly, whose ages were 75 and 77 years. The two genes complement factor H (CFH) and vascular endothelial growth factor A (VEGFA) both had higher expression in the older individuals. They also examined the expression of associated genes in fetal and adult retinal pigment epithelium (RPE). This analysis showed higher complement component 3 (C3) expression in adult RPE compared to fetal RPE. In addition to C3 and CFH, all the complement genes with detectable expression in the retina or RPE experiments showed higher expression levels in tissue from the older individuals.

Anand Swaroop, PhD, chief of a National Eye Institute Laboratory, said, "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 investigators are most likely to find short circuits in DNA that cause AMD. 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."

Related Links:
US National Eye Institute