CFH haplotypes without the Y402H coding variant show strong association with susceptibility to age-relatedmacular degeneration,”Nature

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. Age-related macular degeneration (AMD; OMIM 603075) is a complex degenerative disorder that primarily affects the elderly. Disease susceptibility is influenced by multiple genetic 1-5 and environmental factors After quality assessment of genotype data (see Methods), we tested each SNP for association in 544 unrelated affected individuals and 268 unrelated control