Nature Genetics
- 38, 1049 - 1054 (2006)
Published online: 27 August 2006; | doi:10.1038/ng1871
CFH haplotypes without the Y402H coding variant show strong association with susceptibility to age-related macular degenerationMingyao Li1, 2, Pelin Atmaca-Sonmez3, Mohammad Othman3, Kari E H Branham3, Ritu Khanna3, Michael S Wade4, Yun Li1, Liming Liang1, Sepideh Zareparsi3, 5, Anand Swaroop2, 4 & Gonçalo R Abecasis11
Department of Biostatistics, 1420 Washington Heights, University of Michigan, Ann Arbor, Michigan 48109, USA. 2
Department of Biostatistics and Epidemiology, University of Pennsylvania School of Medicine, 423 Guardian Dr., Philadelphia, Pennsylvania 19104, USA. 3
Department of Ophthalmology and Visual Sciences, W.K. Kellogg Eye Center, 1000 Wall St., Ann Arbor, Michigan 48109, USA. 4
Department of Human Genetics, University of Michigan, 1241 East Catherine St., Ann Arbor, Michigan 48109, USA. 5
Current address: Virginia University Eye Institute, One Stadium Drive, Morgantown, West Virginia 26505, USA.
Correspondence should be addressed to Gonçalo R Abecasis goncalo@umich.edu or Anand Swaroop swaroop@umich.edu 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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