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

被引:291
作者
Zareparsi, S
Branham, KEH
Li, MY
Shah, S
Klein, RJ
Ott, J
Hoh, J
Abecasis, GR
Swaroop, A
机构
[1] Univ Michigan, WK Kellogg Eye Ctr, Dept Ophthalmol & Visual Sci, Ann Arbor, MI 48105 USA
[2] Univ Michigan, Dept Biostat, Ann Arbor, MI 48105 USA
[3] Univ Michigan, Dept Human Genet, Ann Arbor, MI 48105 USA
[4] Rockefeller Univ, Lab Stat Genet, New York, NY 10021 USA
[5] Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06510 USA
关键词
D O I
10.1086/431426
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
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.
引用
收藏
页码:149 / 153
页数:5
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