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Complement Factor H Variant Increases the Risk of Age-Related Macular Degeneration
Jonathan L. Haines,1Michael A. Hauser,2Silke Schmidt,2William K. Scott,2Lana M. Olson,1Paul Gallins,2Kylee L. Spencer,1Shu Ying Kwan,2Maher Noureddine,2John R. Gilbert,2Nathalie Schnetz-Boutaud,1Anita Agarwal,3Eric A. Postel,4Margaret A. Pericak-Vance2*
Age-related macular degeneration (AMD) is a leading cause ofvisual impairment and blindness in the elderly whose etiologyremains largely unknown. Previous studies identified chromosome1q32 as harboring a susceptibility locus for AMD. We used single-nucleotidepolymorphisms to interrogate this region and identified a stronglyassociated haplotype in two independent data sets. DNA resequencingof the complement factor H gene within this haplotype revealeda common coding variant, Y402H, that significantly increasesthe risk for AMD with odds ratios between 2.45 and 5.57. Thiscommon variant likely explains 43% of AMD in older adults.
1 Center for Human Genetics Research, Vanderbilt University Medical Center, Nashville, TN 37232, USA. 2 Center for Human Genetics and Department of Medicine, Duke University Medical Center, DUMC Box 3445, 595 LaSalle Street, Durham, NC 27710, USA. 3 Vanderbilt Eye Institute, Vanderbilt University Medical Center, Nashville, TN 37232, USA. 4 Duke University Eye Center and Department of Ophthalmology, Duke University Medical Center, Durham, NC 27710, USA.
* To whom correspondence should be addressed. E-mail: mpv{at}chg.duhs.duke.edu
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RESEARCH ARTICLES
Robert J. Klein, Caroline Zeiss, Emily Y. Chew, Jen-Yue Tsai, Richard S. Sackler, Chad Haynes, Alice K. Henning, John Paul SanGiovanni, Shrikant M. Mane, Susan T. Mayne, Michael B. Bracken, Frederick L. Ferris, Jurg Ott, Colin Barnstable, and Josephine Hoh (15 April 2005) Science308 (5720), 385.
[DOI: 10.1126/science.1109557] |Abstract »|Full Text »|PDF »|Supporting Online Material »
REPORTS
Albert O. Edwards, Robert Ritter, III, Kenneth J. Abel, Alisa Manning, Carolien Panhuysen, and Lindsay A. Farrer (15 April 2005) Science308 (5720), 421.
[DOI: 10.1126/science.1110189] |Abstract »|Full Text »|PDF »|Supporting Online Material »
PERSPECTIVES
Stephen P. Daiger (15 April 2005) Science308 (5720), 362.
[DOI: 10.1126/science.1111655] |Summary »|Full Text »|PDF »
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