title: CFH haplotypes without the Y402H coding variant show strong association with susceptibility to age-related macular degeneration.
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.
authors.affiliation: Department of Biostatistics, 1420 Washington Heights, University of Michigan, Ann Arbor, Michigan 48109, USA.
authors.forename: Mingyao
authors.initials: M
authors.lastname: Li
authors.forename: Pelin
authors.initials: P
authors.lastname: Atmaca-Sonmez
authors.forename: Mohammad
authors.initials: M
authors.lastname: Othman
authors.forename: Kari E H
authors.initials: KE
authors.lastname: Branham
authors.forename: Ritu
authors.initials: R
authors.lastname: Khanna
authors.forename: Michael S
authors.initials: MS
authors.lastname: Wade
authors.forename: Yun
authors.initials: Y
authors.lastname: Li
authors.forename: Liming
authors.initials: L
authors.lastname: Liang
authors.forename: Sepideh
authors.initials: S
authors.lastname: Zareparsi
authors.forename: Anand
authors.initials: A
authors.lastname: Swaroop
authors.forename: Gonçalo R
authors.initials: GR
authors.lastname: Abecasis
mesh_terms: D000368:Aged; D016022:Case-Control Studies; D017242:Complement Factor H / Q000235:genetics*; D004198:Disease Susceptibility; D005787:Gene Frequency; D006239:Haplotypes; D006801:Humans; D016015:Logistic Models; D008268:Macular Degeneration / Q000235:genetics* / Q000473:pathology; D020641:Polymorphism, Single Nucleotide
chemical_list: D017242:Complement Factor H