Age-related macular degeneration risk

The CFH gene helps calm inflammation in the retina. A common risk variant in it is linked to age-related macular degeneration, a leading cause of vision loss in older adults.

What the CFH Y402H variant does

Complement factor H is the brake on the complement system, the arm of innate immunity that tags and destroys foreign cells. Its job is to stop that machinery from attacking your own tissue. This variant changes one amino acid in the region that binds host surfaces, weakening how well factor H protects the retina from ongoing complement activity.

The result is low-grade chronic inflammation under the macula, which contributes to the drusen deposits and tissue loss of age-related macular degeneration. The discovery of this variant in 2005 is what established complement as central to the disease, and it reoriented the whole field.

How strong the evidence is

This is one of the largest common-variant effects on any common disease. In the catalogued association, based on 2,594 cases and 4,134 controls of European ancestry, the odds ratio was 2.41 per risk copy, with a p-value below 1e-260 and support across multiple independent studies.

For scale, most common disease variants sit between 1.1 and 1.3. An odds ratio above 2 for a single common variant puts this in a small club alongside APOE and Factor V Leiden.

How to read a result here

Age dominates macular degeneration regardless of genotype. It is uncommon before 55 and rises steeply after 75, so a risk genotype at 40 and the same genotype at 78 describe very different situations.

Smoking is the strongest modifiable risk factor and the one that interacts with genetic risk, so stopping is the most useful action available. Regular eye examinations as you age are the other, and sudden distortion of straight lines, a central blur or a blank patch in central vision is an urgent symptom rather than something to monitor at home.

What this variant does not tell you

The other major macular degeneration locus, ARMS2/HTRA1 on chromosome 10, carries an effect of similar size and is not read here. Rare high-impact variants in CFH, CFI, C3 and C9 also exist and are not on consumer chips. A reassuring result at this one position leaves a good deal unread.

It also cannot see your retina. Drusen and early changes are visible on an eye examination long before symptoms, and for people who already have intermediate disease the AREDS antioxidant and zinc formulations reduce progression to the advanced form. That is a decision made with an ophthalmologist, not from a genotype.

What each rs1061170 genotype means

rs1061170 has three possible genotypes: TT, CT and CC.

Lower AMD risk (rs1061170 TT). You carry the lower-risk version of the CFH gene (which helps calm inflammation in the retina) for age-related macular degeneration (AMD), an eye condition that can blur central vision later in life. From what this gene shows your AMD risk is on the lower side.

Higher AMD risk (rs1061170 CT). You carry one copy of the CFH risk variant for age-related macular degeneration, an eye disease of later life. It modestly raises your risk, but it's only one factor: not smoking, eating leafy greens and fish, and regular eye exams as you age all help. It's a tendency, not a diagnosis.

Much higher AMD risk (rs1061170 CC). You have two copies of the CFH risk variant for age-related macular degeneration, which raises your statistical risk more noticeably. Many people with this genotype never develop AMD, and lifestyle (especially not smoking) plus routine eye checkups as you get older make a real difference.

Evidence & sources

Across global populations, about 14% of people carry two copies of this variant, and about 41% carry none.

This variant appears in 3 published genetic studies: PubMed 20385826 · PubMed 21665990 · PubMed 22705344.

Common questions

Does this variant mean I will lose my vision? No. It raises the odds of age-related macular degeneration by about 2.4 times per copy, on a condition that mostly appears after 75, and the majority of people carrying risk copies never develop advanced disease. Not smoking and having your eyes examined as you age are what act on that risk.

Should I take AREDS supplements? That follows an eye examination rather than a genotype. The AREDS formulations were tested in people who already had intermediate macular degeneration, so whether they apply to you depends on what an ophthalmologist sees in your retina.

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