Keeping an eye on the Japanese genome

January 13, 2012
Figure 1: A photograph of a healthy eye. AMD-affected eyes have dark spots that lead to severe visual impairment in the elderly of developed countries. Credit: 2011 iStockphoto/olaaf

Age-related macular degeneration (AMD) is a common disease that can result in blindness. It is caused by cell death in the eye’s retina, which is partly responsible for transforming visual stimuli into electrical signals to the brain. Asian populations tend to exhibit a particular type of the disease, called exudative AMD, which includes changes in the blood vessels of the eye. Caucasians, however, tend to exhibit AMD without these vascular abnormalities. Now, a research team led by Michiaki Kubo at the RIKEN Center for Genomic Medicine in Yokohama has identified four genomic areas that increase the risk for exudative AMD in Japanese individuals.

The researchers searched for genomic regions linked to exudative AMD by investigating single-nucleotide changes in the human genome. They compared the frequencies of 500,000 single-nucleotide changes between individuals with exudative AMD and normal, or control (Fig. 1), individuals. Other research groups had previously performed this kind of genome-wide association study (GWAS) in Caucasian populations, but not in the Japanese.

Kubo and colleagues began by performing a GWAS on 800 Japanese individuals with exudative AMD and 3,000 Japanese controls; they identified two genomic regions previously linked to AMD in Caucasians. This suggested to the researchers that the mechanisms underlying AMD in both populations are likely to be similar.

In a ‘replication study’ using 700 patients and 15,000 controls, the researchers then carefully examined 77 additional genomic areas that showed potential as candidate exudative AMD-associated regions in their initial GWAS. The replication study yielded two additional genomic regions that were linked to exudative AMD. One of these—on chromosome 4—covered four nearby genes, so the researchers were unable to pinpoint with certainty which of the genes were responsible for the disease risk. However, another region—on chromosome 8—was linked to the gene called TNFRSF10A, which encodes a receptor expressed in the eye that modulates inflammation and

The variant of the gene that Kubo and colleagues linked to exudative AMD seemed to regulate the expression of the receptor. “We are next planning to investigate exactly how the signaling pathway initiated by this receptor would affect the development of exudative AMD,” explain Kubo and Satoshi Arakawa, the study’s first author.

The identification of these that are linked to exudative AMD could aid in the development of new therapies. “Our results will also help in the construction of risk prediction models for exudative AMD,” say Kubo and Arakawa.

Explore further: Gene variant increases risk of blindness

More information: Nature Genetics 43, 1001–1004 (2011) doi:10.1038/ng.938

Related Stories

Gene variant increases risk of blindness

July 18, 2007

Researchers have found a gene variant that can more than double the risk of developing the degenerative eye disease, age-related macular degeneration.

A break for bone disease research

July 29, 2011

Osteoporosis is the reduction in bone strength that occurs during aging, which increases the chance of elderly people experiencing breaks. A genome-wide association study in the Japanese population has revealed that a genomic ...

Recommended for you

Zika virus may persist in the vagina days after infection

August 25, 2016

The Zika virus reproduces in the vaginal tissue of pregnant mice several days after infection, according to a study by Yale researchers. From the genitals, the virus spreads and infects the fetal brain, impairing fetal development. ...

In sub-Saharan Africa, cancer can be an infectious disease

August 26, 2016

In 1963, Irish surgeon Denis Parson Burkitt airmailed samples of an unusual jaw tumor found in Ugandan children to his colleague, Anthony Epstein, at Middlesex Hospital in London. Epstein, an expert in chicken viruses and ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.