Protective Variants Could Shield Against Age-related Macular Degeneration

Age-related macular degeneration (AMD) is a common eye condition causing blurriness in central vision due to damage to the macula, a small region in the center of the retina. The macula is responsible for the sharp, detailed central vision needed for tasks such as reading and driving. This ailment typically affects individuals over the age of 55 and is categorized into two types: dry and wet AMD.

Dry AMD is a gradual process where the macula thins over time due to aging, whereas wet AMD occurs more rapidly, often instigated by abnormal blood vessels damaging the macula.

Macular degeneration
Macular degeneration. BruceBlaus via Wikipedia. CC-Attribution-Share Alike 4.0 International

Recognizing AMD can be challenging, especially in its early and intermediate stages when AMD is typically asymptomatic. Vision distortions, central vision reduction, and blurriness usually appear in advanced stages when treatment options are limited. Wet AMD has better treatment prognosis than dry AMD. 

While the condition can affect anyone, it’s more prevalent among individuals who have a familial history of the condition. Smoking can also enhance the risk of developing AMD. Regardless of risk factors, it is important to schedule regular eye check-ups, including dilated eye exams, to detect AMD and other eye conditions early.

Experts propose that both genetic and environmental factors contribute to AMD. A study published in BMC Genetics analyzed genetic variants previously associated with the condition and identified two potentially protective variants.

You can use the Nebula Genome Browser to see if you have these protective gene variants. Keep reading to learn what these mutations are and how you can check your status.

The Study

In this study, researchers systematically reviewed existing literature sources to identify candidate protective variants (CPVs). However, as they did not test these variants for functionality, they couldn’t conclusively establish whether they provide a protective effect. Thus, they use the term “candidate” protective variants. 

The authors concentrated their analysis on variants that alter the amino acid sequence of proteins, thereby increasing the probability of finding functional CPVs. This process can help experts narrow down which variants may be good candidates for further characterization and clinical trials.


Starting with 19 AMD susceptibility loci from previous genome-wide association studies, the researchers searched for variants linked to AMD within nearby genes. This search yielded eight relevant variants from six chromosomal loci. From these eight, they further analyzed two variant alleles that displayed evidence of positive selection, a strong indicator of a protective effect. Positive selection describes a process where variants that protect against disease become more common in a population over time.

These two variants alleles are E318D found on the C2 gene and R32Q on the CFB gene. Using data from previous studies, the authors estimated that individuals with both protective alleles are ten times less likely to develop AMD than those without either allele.

Illustration of dry AMD
Illustration of dry AMD. Flickr. Public Domain

To ascertain if you carry these potentially protective alleles, follow the steps below. However, please note that the authors of this study did not perform experiments to validate the protective effect or uncover its molecule mechanisms.

Explore your Genome!

Did you know you can use the Nebula Genome Browser (available with Deep and Ultra Deep WGS) to check whether you have protective variants?

  1. Go to the Genome Browser. In the top left corner of the genome browser, you can find a search bar.
  2. The authors identified independent variants in the C2 and CFB genes that contribute to protection. The rsID for E318D (C2) is rs9332739 and R32Q (CFB) is rs641153
  3. Using the dbSNP database, you can find that the genome coordinates in the format [chromosome number][chromosome location] are 6:31936027 and 6:31946403 (GRCh38 reference genome).
  4. Copy-paste this location into the search bar and press enter. 
  5. The genome browser will now zoom in on these locations. 
  6. Activate the “Center Line” in the bar at the top to better see the location that you are looking at.
  7. You should see stacked, gray stripes. Those are your personal DNA sequencing reads that are aligned to a reference genome sequence (colored letters above). If your DNA sequence matches the reference, then the stripes are gray. If the sequence is somehow different from the reference, then you will see various letters and symbols in different colors.
  8. For the variant rs9332739, you have a protective allele if you see a C (instead of the reference G allele indicated by gray stripes). For the variant rs641153, you have a protective allele if you see an A (instead of the reference G allele). Remember that the protective alleles are only extra protection! The group that doesn’t have them is at no greater risk than the general population.


Butler, J.M., Hall, N., Narendran, N. et al. Identification of candidate protective variants for common diseases and evaluation of their protective potential. BMC Genomics 18, 575 (2017).

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