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

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 ( x(2)=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.