| Health / Health News |
New study about genes linked to age-related macular degeneration
National Eye Institute scientists led a collaborative study and zeroed in on genes associated with age-related macular degeneration (AMD), a leading cause of vision loss and blindness among people age 65 and older.
AMD causes the loss of cell function in the macula, the area of the retina required for seeing details in one’s central area of vision. Photo: NEI
Previously, Anand Swaroop, Ph.D., chief of the Neurobiology-Neurodegeneration and Repair Laboratory at National Eye Institute and colleagues had compared populations of people with and without AMD and identified 34 small genomic regions—called loci—and 52 genetic variants within these loci that were significantly associated with AMD. “However, as with other common and complex diseases, most of the variants turned out not to be present in protein-coding regions of the genome, leaving us to wonder how they were having a biological effect on AMD,” said Swaroop.
The researchers explored whether the variants might regulate AMD-relevant genes, possibly at promoters, which are sequences within DNA that turn genes on, or enhancers, which increase the activity of promoters.
They studied 453 retinas, the eye tissue affected by AMD, from deceased human donors with and without AMD. The analysis involved sequencing each retina’s ribonucleic acid (RNA), the messenger molecule that carries instructions from DNA for making proteins.
To search for the genetic variants regulating gene expression in the retina, they used expression quantitative trait loci (eQTL) analysis. Computational methods allowed the researchers to detect patterns between the genes expressed in the retina and a pool of more than 9 million previously identified genetic variants.
Specifically, they looked for variants with a high probability of being responsible for variations in gene expression among people with and without AMD. The analysis pointed to target disease genes at six of the 34 AMD loci identified in the earlier research.
In addition, integration of this data with earlier AMD studies identified three additional target AMD genes, which had never before been shown to play a role in AMD. This analysis also suggested as many as 20 additional candidate genes providing insights into the genes and pathways involved in pathobiology of AMD.
Among the most plausible target genes were B3GLCT and BLOC1S1, which could affect AMD-related cell functions such as signaling; the breakdown and disposal of unwanted proteins; and the stability of the extracellular matrix, the cell’s infrastructure for distribution.
AMD is a complex disease influenced by yet-to-be-understood mix of genetic and behavioral factors. Smoking, for example, increases the risk of developing the disease, while eating leafy greens and fish reduces it. More research is needed to understand how these environmental factors interact with genes to contribute to the development of the disease and its severity. (National Institutes of Health)
YOU MAY ALSO LIKE
