Genetics of age-related macular degeneration (AMD)

Hum Mol Genet. 2017 Aug 1;26(R1):R45-R50. doi: 10.1093/hmg/ddx228.


Age-related macular degeneration (AMD) is a progressive blinding disease and represents the leading cause of visual impairment in the aging population. AMD affects central vision which impairs one's ability to drive, read and recognize faces. There is no cure for this disease and current treatment modalities for the exudative form of the disease require repeated intravitreal injections which may be painful, are incompletely efficacious, and represent a significant treatment burden for both the patient and physician. As such, AMD represents a significant and important clinical problem.It is anticipated that in three years' time, 196 million individuals will be affected with AMD. Over 250 billion dollars per year are spent on care for AMD patients in the US. Over half of the heritability is explained by two major loci, thus AMD is considered the most well genetically defined of the complex disorders. A recent GWAS on 43,566 subjects identified novel loci and pathways associated with AMD risk, which has provided an excellent platform for additional functional studies. Genetic variants have been investigated, particularly with respect to anti-VEGF treatment, however to date, no pharmacogenomic associations have been consistently identified across these studies. It may be that if the goal of personalized medicine is to be realized and biomarkers are to have predictive value for determining the magnitude of risk for AMD at the genetic level, one will need to examine the relationships between these pathways across disease state and relative to modifiable risk factors such as hypertension, smoking, body mass index, and hypercholesterolemia. Further studies investigating protective alleles in populations with low AMD prevalence may lead to this goal.

Publication types

  • Review
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Genetic Predisposition to Disease / genetics
  • Genetic Therapy
  • Genome-Wide Association Study
  • Humans
  • Macular Degeneration / genetics*
  • Macular Degeneration / metabolism
  • Precision Medicine
  • Risk Factors