Macular degeneration research gets a boost from large gene study

The findings of a large gene study are a big step forward for research into age-related macular degeneration – a leading cause of vision loss in the over-50s.
The researchers found 52 common and rare genetic variants linked to AMD – a leading cause of vision loss in the over-50s.

Age-related macular degeneration (AMD) is a progressive eye disease that damages the macula – the small area of the retina that is needed for sharp, central vision.

As AMD progresses, it becomes increasingly difficult to do everyday things like read, write, drive and recognize faces.

The international study, published in the journal Nature Genetics, significantly expands the number of genetic factors known to be involved in the development of AMD.

Researchers from the International AMD Genomics Consortium collected and analyzed the genetic data from 43,566 people of predominantly European descent and found 52 common and rare variants linked to AMD.

Co-senior author Jonathan L. Haines, a professor of genomic studies at Case Western Reserve University in Cleveland, OH, says:

“These variants provide a foundation for genetic studies of AMD going forward.”

He and his colleagues suggest the findings should improve our understanding of the biology of AMD and help develop new drugs for the disease, which destroys retinal photoreceptors – the light-sensitive cells at the back of the eye.

34 known regions of genome linked to AMD

The Food and Drug Administration (FDA) currently have no approved treatments for the more common form of advanced AMD, called geographic atrophy, or “dry” AMD.

While FDA-approved drugs for the other advanced form of AMD – called neovascular, or “wet” AMD – can arrest the growth of abnormal, leaky blood vessels at the back of the eye, they do not cure the disease and do not work for all patients.

The risk of developing AMD depends on a combination of genes, environment and lifestyle. Studies show that smoking raises the risk, while eating leafy green vegetables and some types of fish – including tuna, halibut and salmon – reduces the risk.

Before the new study, scientists knew of 21 regions of the genome that contain sequences of DNA whose variations affect the risk of developing AMD. The new study brings that number to 34.

For the study, the team analyzed the DNA of about 23,000 people with AMD and 20,000 without it. Their analysis covered most of the genome in each case, focusing mostly on regions already known or thought to be linked to AMD.

They compared the results with reference DNA data held in the 1000 Genomes project. This yielded over 12 million potential genetic variants.

52 variants from 12 million potentials

The researchers then looked again at the DNA samples from the study participants to see how often these 12 million variants occurred in people with and without AMD.

Altogether, they pinpointed 52 common and rare genetic variants linked to AMD. Common variants generally have an indirect link with a disease, while rare variants – defined as those occurring in less than 1% of the study population – generally have a direct or causal link. This is because they are more likely to change the way the associated protein behaves.

Prof. Haines concludes:

“The next step is to investigate what the variants are doing to the genes and how they affect gene function. Do they turn them on or off? Do they interact with other genes spurring a series of events along a pathway that leads to AMD?”

One of the findings confirms an already established link between AMD and two genes – CFH and TIMP3. CFH was one of the first to be identified through genome-wide association studies, while TIMP3 is known to be linked to Sorsby’s fundus dystrophy, a rare disease similar to AMD that tends to affect people before they reach middle-age.

The researchers also discovered – for the first time – a variant linked to wet AMD that may explain why drugs for this advanced form of the disease do not work for all patients.

Ten of the genes the researchers found appear to be involved in maintaining the extracellular matrix – the material that supports and feeds the cells of the eye. Previous studies have suggested problems in the extracellular matrix are linked to some AMD cases that develop without early-stage signs, or that deteriorate rapidly before signs are apparent.

The researchers note that while their study pooled data from a very large population, it is unlikely they have found all the variants that account for the heritability of AMD – but the findings are a significant advance in that direction.

According to the National Eye Institute, who part-funded the study, by 2050, the estimated number of Americans with AMD is expected to more than double from 2.07 million to 5.44 million.

Meanwhile, Medical News Today recently learned of a study published in The American Journal of Medicine that suggests AMD may be treatable with a Parkinson’s drug. From an analysis of thousands of medical records, researchers found that patients receiving L-DOPA – a drug commonly used to treat Parkinson’s disease – were significantly less likely to develop AMD, and when they did, it began much later.

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