Complement factor H variant increases the risk of age-related macular degeneration

Science. 2005 Apr 15;308(5720):419-21. doi: 10.1126/science.1110359. Epub 2005 Mar 10.


Age-related macular degeneration (AMD) is a leading cause of visual impairment and blindness in the elderly whose etiology remains largely unknown. Previous studies identified chromosome 1q32 as harboring a susceptibility locus for AMD. We used single-nucleotide polymorphisms to interrogate this region and identified a strongly associated haplotype in two independent data sets. DNA resequencing of the complement factor H gene within this haplotype revealed a common coding variant, Y402H, that significantly increases the risk for AMD with odds ratios between 2.45 and 5.57. This common variant likely explains approximately 43% of AMD in older adults.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aged
  • Alleles
  • Binding Sites
  • C-Reactive Protein / metabolism
  • Case-Control Studies
  • Chromosomes, Human, Pair 1 / genetics
  • Complement Activation
  • Complement Factor H / analysis
  • Complement Factor H / genetics*
  • Complement Factor H / physiology
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Genetic Variation*
  • Genotype
  • Haplotypes
  • Heparin / metabolism
  • Humans
  • Linkage Disequilibrium
  • Macular Degeneration / genetics*
  • Odds Ratio
  • Polymorphism, Single Nucleotide*
  • Risk Factors
  • Sequence Analysis, DNA
  • Smoking


  • CFH protein, human
  • Complement Factor H
  • Heparin
  • C-Reactive Protein