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Submitted on January 10, 2005
Accepted on February 22, 2005
Complement Factor H Polymorphism in Age-Related Macular Degeneration
Robert J. Klein 1, Caroline Zeiss 2, Emily Y. Chew 3, Jen-Yue Tsai 4, Richard S. Sackler 1, Chad Haynes 1, Alice K. Henning 5, John Paul SanGiovanni 3, Shrikant M. Mane 6, Susan T. Mayne 7, Michael B. Bracken 7, Frederick L. Ferris 3, Jurg Ott 1, Colin Barnstable 2, Josephine Hoh 7*
1 Laboratory of Statistical Genetics, Rockefeller University, 1230 York Avenue, New York, NY 10021, USA. 2 Department of Ophthalmology and Visual Science, Yale University School of Medicine, 330 Cedar Street, New Haven, CT 06520, USA. 3 National Eye Institute, Building #10, CRC, 10 Center Drive, Bethesda, MD 20892-1204, USA. 4 Biological Imaging Core, National Eye Institute, 9000 Rockville Pike, Bethesda, MD 20892, USA. 5 The EMMES Corporation, 401 North Washington Street, Suite 700, Rockville MD 20850, USA. 6 W.M. Keck Facility, Yale University, 300 George Street, Suite 201, New Haven, CT 06511, USA. 7 Department of Epidemiology and Public Health, Yale University School of Medicine, 60 College Street, New Haven CT 06520, USA.
* To whom correspondence should be addressed.
Josephine Hoh , E-mail: josephine.hoh{at}yale.edu
Age-related macular degeneration (AMD) is a major cause of blindnessin the elderly. We report a genome-wide screen of 96 cases and50 controls for polymorphisms associated with AMD. Among 116,204SNPs genotyped, an intronic and common variant in the complementfactor H gene (CFH) is strongly associated with AMD (nominalP value <10-7). Individuals homozygous for the risk alleleshave a 7.4-fold increased likelihood of AMD (95% CI 2.9 to 19).Resequencing revealed a polymorphism in linkage disequilibriumwith the risk allele representing a tyrosine-histidine changeat amino acid 402. This polymorphism is in a region of CFH thatbinds heparin and C-reactive protein. The CFH gene is locatedon chromosome 1 in a region repeatedly linked to AMD in family-basedstudies.
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