Skip to content
Use your HSA or FSA funds

Condition report · Ophthalmological

Age-Related Macular Degeneration

Whole genome sequencing evaluates all AMD-associated genes (CFH, ARMS2/HTRA1, C3, CFB, C2, CFI, TIMP3), providing the genetic risk profile that informs screening intensity, lifestyle modification urgency, and eligibility for complement-targeted therapies.

A condition report looks for rare variants known to cause the conditions it covers.

Included in Premium and Premium + AI

Premium adds $99 per kit for the first year.

Order with Premium

About this condition

A common eye condition of later life that damages the macula, the part of the retina responsible for sharp central vision. Both genetic factors (such as CFH and ARMS2) and lifestyle factors such as smoking contribute to the risk.

Age-related macular degeneration (AMD) is the leading cause of central vision loss in adults over 50, affecting approximately 11 million Americans. AMD has one of the highest heritabilities of any common disease, approximately 46-71%. The complement factor H (CFH) Y402H variant (rs1061170) on chromosome 1q31.3 is the strongest single genetic risk factor: carriers have approximately 2.5-7x increased risk depending on genotype (heterozygous ~2.5x, homozygous ~5-7x). The second major locus is ARMS2/HTRA1 on chromosome 10q26, conferring ~2.5-3x risk per allele. Together, CFH and ARMS2/HTRA1 explain approximately 50% of AMD heritability.

The complement pathway has become a therapeutic target for AMD. Pegcetacoplan (Syfovre) and avacincaptad pegol (Izervay), both complement inhibitors (C3 and C5 inhibitors respectively), received FDA approval in 2023 for geographic atrophy (GA), the advanced dry form of AMD for which no treatment previously existed. These complement-targeted therapies slow GA progression by approximately 20-30%. Genetic complement variant status (CFH, C3, CFB genotypes) may influence treatment response; preliminary evidence suggests that patients with certain CFH risk genotypes may have differential complement inhibitor responses, though this pharmacogenomic application is still being validated.

Additional AMD susceptibility genes include C3 (complement component 3, rare risk variants with strong effect), CFB (complement factor B), C2 (complement component 2), CFI (complement factor I), and TIMP3 (tissue inhibitor of metalloproteinases 3). TIMP3 also causes Sorsby fundus dystrophy, a monogenic AMD mimic. ABCA4 (Stargardt disease) can mimic AMD in adults, and BEST1 (Best disease) is another AMD mimic. Distinguishing polygenically-driven AMD from monogenic macular dystrophies that mimic AMD (Stargardt, Sorsby, Best disease) has important implications: monogenic conditions have specific treatments, earlier onset, and Mendelian recurrence risks.

Complement inhibitors (pegcetacoplan, avacincaptad) are the first FDA-approved treatments for geographic atrophy, the advanced dry AMD for which no treatment existed before 2023. CFH genotype may predict treatment response.

The 2 conditions we analyse

Age-Related Macular Degeneration

A progressive degeneration of the macula in older adults, occurring in dry (atrophic) and wet (neovascular) forms.

What a diagnosis changes

AREDS2 supplementation; anti-VEGF injections (ranibizumab, aflibercept) for wet AMD; pegcetacoplan (Syfovre) for geographic atrophy; avacincaptad (Izervay) for GA; smoking cessation; blood pressure management; UV protection; low-vision rehabilitation

Genes analysed

Also known as

AMD; ARMD; Senile macular retinal degeneration

Includes 15 related subtypes ↓
  • age related macular degeneration 1
  • age related macular degeneration 10
  • age related macular degeneration 11
  • age related macular degeneration 12
  • age related macular degeneration 14
  • age related macular degeneration 2
  • age related macular degeneration 4
  • age related macular degeneration 6
  • age related macular degeneration 7
  • age related macular degeneration 8
  • age related macular degeneration 9
  • dry age related macular degeneration
  • macular degeneration, age-related, 3
  • macular dystrophy with central cone involvement
  • wet macular degeneration
MONDO:0005150Orphanet 279MedGen 116576

Basal Laminar Drusen

Autosomal dominant

An early-onset form of drusen, often linked to changes in CFH, that can resemble and progress like age-related macular degeneration.

Genes analysed

Also known as

drusen of Bruch membrane

MONDO:0007472OMIM 126700MedGen 152676

Why whole genome sequencing

AMD is the leading cause of central vision loss with 70% heritability. Complement-targeted therapies are now available, and genetic risk profiling guides screening intensity, lifestyle intervention urgency, and may predict therapy response.

CFH genotype may predict complement inhibitor response: precision AMD therapy is emerging

Preliminary pharmacogenomic data suggests that AMD patients with specific CFH, C3, and CFB genotypes may respond differently to complement-targeted therapies. While these associations are still being validated in clinical trials, establishing a patient's complement gene genotype through WGS provides the genetic data needed for future pharmacogenomic-guided AMD therapy selection. Additionally, high-risk CFH genotypes identify individuals who benefit most from aggressive modifiable risk factor management (smoking cessation, AREDS2 supplementation, blood pressure control).

Monogenic macular dystrophies (Stargardt, Best, Sorsby) mimic AMD but have different treatments and genetic counseling implications

Adult-onset Stargardt disease (ABCA4), Best disease (BEST1), and Sorsby fundus dystrophy (TIMP3) can present with macular degeneration clinically indistinguishable from AMD. These monogenic conditions have Mendelian inheritance (50% risk to offspring for dominant conditions), potentially different treatment responses, and, for Stargardt, eligibility for emerging gene therapy trials. WGS distinguishes these monogenic mimics from typical polygenic AMD, enabling accurate genetic counseling and appropriate treatment selection.

Other ophthalmological conditions

All conditions →

One test. A lifetime of answers.

One kit, sent to your home. Your entire genome sequenced at the clinical standard used for diagnostic decisions. Physician-ready reports delivered to your Genome Manager in 6–8 weeks — permanent and updated as science advances.

From $449

Free shipping · Results in 6–8 weeks

Premium adds $99 per kit for the first year.

Order with Premium