Age-related macular degeneration

Age-related macular degeneration is a common cause of central vision loss in older adults. This score sums common variants that nudge that risk up or down.

What this macular degeneration score reads

This is PGS002269, a 47-variant score used by Zekavat and colleagues in a 2022 Ophthalmology study of retinal layer thinning in UK Biobank, built from age-related macular degeneration GWAS data on 33,976 people of European ancestry.

Its largest weights sit in the complement pathway, in CFH, CFI and C3, along with the ARMS2/HTRA1 locus on chromosome 10. Those two regions, complement factor H and ARMS2, dominate the common-variant genetics of this condition more than is usual for a complex disease.

What the published evidence for this score actually is

This is worth being precise about. The performance recorded for this score in the PGS Catalog is its association with retinal layer thickness on optical coherence tomography, where each standard deviation higher score corresponded to a 0.21 standard deviation thinner photoreceptor layer in 44,253 people.

That is a biomarker of early disease, not a measured ability to predict who develops macular degeneration or loses vision. The score is built from well-established risk variants, so it plausibly tracks risk, but the published validation attached to it is about retinal thinning rather than diagnosis.

How to read a high or low score

Ten of the 47 variants cannot be read from a consumer DNA file, including several sizeable complement weights, so any percentile from one is a partial version of the score.

Age dominates this condition: it is uncommon before 55 and rises steeply thereafter. The practical response to a high score is unexciting and effective: regular eye examinations as you age, and taking sudden distortion of straight lines, a central blur or a blank patch in central vision seriously as an urgent symptom rather than a nuisance.

What matters more than this score

Smoking is the strongest modifiable risk factor for macular degeneration, and it interacts with the ARMS2 risk variants rather than simply adding to them, so the combination is worse than either alone. Stopping smoking is the single most useful thing available here.

For people who already have intermediate disease in an eye examination, specific antioxidant and zinc supplement formulations tested in the AREDS trials reduce progression to the advanced form, but that is a decision made with an ophthalmologist on the basis of an examination, not on a genetic percentile.

Ancestry and accuracy

The GWAS behind this score was entirely European ancestry, and macular degeneration frequencies and genetic risk profiles differ across populations. A percentile computed for someone of non-European ancestry rests on no validation at all.

Variants in this score you can read on their own

This score includes a variant that this site also explains individually, where you can see what each genotype means on its own: APOE type (Alzheimer's & cholesterol) (rs429358).

How much of this score your file covers

37 of the published score's 47 variants are present in a standard consumer DNA file (79%). The remaining 10 cannot be read from one, so a result computed here approximates the published score rather than reproducing it.

Common questions

Is macular degeneration inherited? It has one of the stronger common-variant components among age-related diseases, concentrated in the complement pathway and the ARMS2 region. That still leaves age and smoking as the largest determinants of who develops it.

Should I take AREDS supplements because my score is high? That decision follows an eye examination, not a genetic score. The AREDS formulations were tested in people who already had intermediate macular degeneration, and taking them is a conversation to have with an ophthalmologist who has looked at your retina.

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