Strong association of the Y402H variant in complement factor H at 1q32 with susceptibility to age-related macular degeneration

Am J Hum Genet. 2005 Jul;77(1):149-53. doi: 10.1086/431426. Epub 2005 May 13.


Using a large sample of cases and controls from a single center, we show that a T-->C substitution in exon 9 (Y402H) of the complement factor H gene is strongly associated with susceptibility to age-related macular degeneration, the most common cause of blindness in the elderly. Frequency of the C allele was 0.61 in cases, versus 0.34 in age-matched controls (P<1x10(-24)). Genotype frequencies also differ markedly between cases and controls (chi2=112.68 [2 degrees of freedom]; P<1x10(-24)). A multiplicative model fits the data well, and we estimate the population frequency of the high-risk C allele to be 0.39 (95% confidence interval 0.36-0.42) and the genotype relative risk to be 2.44 (95% confidence interval 2.08-2.83) for TC heterozygotes and 5.93 (95% confidence interval 4.33-8.02) for CC homozygotes.

Publication types

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

MeSH terms

  • Aged
  • Case-Control Studies
  • Chromosomes, Human, Pair 1
  • Complement Factor H / genetics*
  • Gene Frequency
  • Genetic Predisposition to Disease*
  • Humans
  • Macular Degeneration / genetics*
  • Models, Genetic
  • Polymorphism, Genetic*
  • Risk


  • CFH protein, human
  • Complement Factor H