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Complement Factor H Polymorphism in Age-Related Macular Degeneration
Robert J. Klein,1Caroline Zeiss,2*Emily Y. Chew,3*Jen-Yue Tsai,4*Richard S. Sackler,1Chad Haynes,1Alice K. Henning,5John Paul SanGiovanni,3Shrikant M. Mane,6Susan T. Mayne,7Michael B. Bracken,7Frederick L. Ferris,3Jurg Ott,1Colin Barnstable,2Josephine Hoh7
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 116,204single-nucleotide polymorphisms genotyped, an intronic and commonvariant in the complement factor H gene (CFH) is strongly associatedwith AMD (nominal P value <10-7). In individuals homozygousfor the risk allele, the likelihood of AMD is increased by afactor of 7.4 (95% confidence interval 2.9 to 19). Resequencingrevealed a polymorphism in linkage disequilibrium with the riskallele representing a tyrosine-histidine change at amino acid402. This polymorphism is in a region of CFH that binds heparinand C-reactive protein. The CFH gene is located on chromosome1 in a region repeatedly linked to AMD in family-based studies.
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.
* These authors contributed equally to this work.
To whom correspondence should be addressed. E-mail: josephine.hoh{at}yale.edu
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[DOI: 10.1126/science.1110189] |Abstract »|Full Text »|PDF »|Supporting Online Material »
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Long-term Vision Rescue by Human Neural Progenitors in a Rat Model of Photoreceptor Degeneration.
S. Wang, S. Girman, B. Lu, N. Bischoff, T. Holmes, R. Shearer, L. S. Wright, C. N. Svendsen, D. M. Gamm, and R. D. Lund (2008)
Invest. Ophthalmol. Vis. Sci.
49, 3201-3206
|Abstract »|Full Text »|PDF »
Genetic model selection in two-phase analysis for case-control association studies.
Genotype-Phenotype Correlations for Exudative Age-Related Macular Degeneration Associated with Homozygous HTRA1 and CFH Genotypes.
N. Leveziel, J. Zerbib, F. Richard, G. Querques, G. Morineau, V. Fremeaux-Bacchi, G. Coscas, G. Soubrane, P. Benlian, and E. H. Souied (2008)
Invest. Ophthalmol. Vis. Sci.
49, 3090-3094
|Abstract »|Full Text »|PDF »
AMD-like Lesions in the Rat Retina: A Latent Consequence of Perinatal Hemorrhage.
D. V. Pow and C. M. Diaz (2008)
Invest. Ophthalmol. Vis. Sci.
49, 2790-2798
|Abstract »|Full Text »|PDF »
Altered Function of Factor I Caused by Amyloid {beta}: Implication for Pathogenesis of Age-Related Macular Degeneration from Drusen.
J. Wang, K. Ohno-Matsui, T. Yoshida, A. Kojima, N. Shimada, K.-i. Nakahama, O. Safranova, N. Iwata, T. C. Saido, M. Mochizuki, et al. (2008)
J. Immunol.
181, 712-720
|Abstract »|Full Text »|PDF »
Microarray Technology and Applications in the Arena of Genome-Wide Association.
R. D. Jager, W. F. Mieler, and J. W. Miller (2008)
N. Engl. J. Med.
358, 2606-2617
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Association Analysis of CFH, C2, BF, and HTRA1 Gene Polymorphisms in Chinese Patients with Polypoidal Choroidal Vasculopathy.
K. Y. Lee, E. N. Vithana, R. Mathur, V. H. Yong, I. Y. Yeo, A. Thalamuthu, M.-W. Lee, A. H. Koh, M. C. Lim, A. C. How, et al. (2008)
Invest. Ophthalmol. Vis. Sci.
49, 2613-2619
|Abstract »|Full Text »|PDF »
Late Outgrowth Endothelial Progenitor Cells in Patients with Age-Related Macular Degeneration.
M. Thill, N. V. Strunnikova, M. J. Berna, N. Gordiyenko, K. Schmid, S. W. Cousins, D. J. S. Thompson, and K. G. Csaky (2008)
Invest. Ophthalmol. Vis. Sci.
49, 2696-2708
|Abstract »|Full Text »|PDF »
Racial Differences and Other Risk Factors for Incidence and Progression of Age-Related Macular Degeneration: Salisbury Eye Evaluation (SEE) Project.
M. A. Chang, S. B. Bressler, B. Munoz, and S. K. West (2008)
Invest. Ophthalmol. Vis. Sci.
49, 2395-2402
|Abstract »|Full Text »|PDF »
Ceruloplasmin/Hephaestin Knockout Mice Model Morphologic and Molecular Features of AMD.
M. Hadziahmetovic, T. Dentchev, Y. Song, N. Haddad, X. He, P. Hahn, D. Pratico, R. Wen, Z. L. Harris, J. D. Lambris, et al. (2008)
Invest. Ophthalmol. Vis. Sci.
49, 2728-2736
|Abstract »|Full Text »|PDF »
Estrogen Receptor Alpha and Matrix Metalloproteinase 2 Polymorphisms and Age-related Maculopathy in Older Women.
R. L. Seitzman, V. B. Mahajan, C. Mangione, J. A. Cauley, K. E. Ensrud, K. L. Stone, S. R. Cummings, M. C. Hochberg, T. A. Hillier, J. S. Sinsheimer, et al. (2008)
Am. J. Epidemiol.
167, 1217-1225
|Abstract »|Full Text »|PDF »
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