CFH haplotypes without the Y402H coding variant show strong association with susceptibility to age-related macular degeneration - PubMed (original) (raw)

Comparative Study

. 2006 Sep;38(9):1049-54.

doi: 10.1038/ng1871. Epub 2006 Aug 27.

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Comparative Study

Mingyao Li et al. Nat Genet. 2006 Sep.

Abstract

In developed countries, age-related macular degeneration is a common cause of blindness in the elderly. A common polymorphism, encoding the sequence variation Y402H in complement factor H (CFH), has been strongly associated with disease susceptibility. Here, we examined 84 polymorphisms in and around CFH in 726 affected individuals (including 544 unrelated individuals) and 268 unrelated controls. In this sample, 20 of these polymorphisms showed stronger association with disease susceptibility than the Y402H variant. Further, no single polymorphism could account for the contribution of the CFH locus to disease susceptibility. Instead, multiple polymorphisms defined a set of four common haplotypes (of which two were associated with disease susceptibility and two seemed to be protective) and multiple rare haplotypes (associated with increased susceptibility in aggregate). Our results suggest that there are multiple disease susceptibility alleles in the region and that noncoding CFH variants play a role in disease susceptibility.

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Figures

Figure 1

Figure 1

P values for single-SNP association, when comparing unrelated affected individuals (cases) and controls. The dotted horizontal line is −log10(P) of the original Y402H variant (circled in blue). Strongly associated SNPs fall into one of two LD groups (SNPs in one of these groups are colored in green; SNPs in the other group are colored in purple; SNPs outside either group are in black). SNPs selected from the stepwise haplotype association analysis are circled in red. Linkage disequilibrium across the CFH region is shown below, plotted as pairwise _r_2 values.

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