Rare and common genetic faults that affect the risk of age-related macular degeneration.

A new study of more than 43,000 people has found 52 genetic risk factors for age-related macular degeneration (AMD). They include the first link that’s specific to ‘wet’ AMD, near the gene known as MMP9.

Advanced AMD is the leading cause of sight loss in older people. It affects 1 in 20 people over the age of 75. We already know that environmental factors such as ethnic origin and smoking affect the risk of getting AMD, as well as several known genetic links. But the new study is the largest of its kind by far and has turned up some important new information.

The large international team of researchers involved in the study used a range of way to investigate the genetics of AMD, from scanning across the whole genome to targeting known genetic locations. In all, they looked at over 12 million genetic variants.

Wet and dry share their genes

Results showed that both wet and dry types of AMD largely share their genetics. This means that people at high risk of wet AMD are just as likely to get dry AMD and vice versa. So any treatment that targets one but not the other could still leave the patient at risk of sight loss from the other type of AMD.

The team also found some very rare variations in the genes CFH, CFI AND TIMP3 that suggest faults in these genes can cause AMD, as can faults in the gene SLC168A. However, the more common variations were responsible for the greatest risk. Forty-five of the 52 risk factors were common, and 7 were rare.

Lower risk

Participants in the study were largely of European origin, but the rare variants were also found to be rare in participants of other ethnicities. Two of the rare variants in CFH were linked to a lower risk of AMD.

“This is important research, not just because it identifies new causal genes for AMD and therefore new disease mechanisms and potential targets for treatment,” said Dr Dolores M Conroy, Director of Research at Fight for Sight. “The results also point to the way in which future research needs to be done to have any chance of tracking down all of the genetic risk factors.

“Some of the variants found in this study are extremely rare, occurring in fewer than 1 in 1000 people with AMD. So if we find several of these rare variants in different people at the same location, they can pinpoint the gene that’s causing disease. But because they’re so rare it means we will need vast numbers of study participants to identify genetic locations that are currently unknown.”

The results were published in the journal Nature Genetics.