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Abstract

Age-related macular degeneration (AMD) is a common, late-onset, and complex trait with multiple risk factors. Concentrating on a region harboring a locus for AMD on 1q25-31, the ARMD1 locus, we tested single-nucleotide polymorphisms for association with AMD in two independent case-control populations. Significant association (P = 4.95 × 10-10) was identified within the regulation of complement activation locus and was centered over a tyrosine-402 → histidine-402 protein polymorphism in the gene encoding complement factor H. Possession of at least one histidine at amino acid position 402 increased the risk of AMD 2.7-fold and may account for 50% of the attributable risk of AMD.
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Present address: Institute for Retina Research, 3215 Princess Lane, Dallas, TX 75229, USA.

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We thank the McDermott Sequencing Center at UTSWMC for genotyping assistance and T. Hyatt for technical advice and assistance. Supported by the National Eye Institute (EY014467), a center grant from the Foundation Fighting Blindness, and Research to Prevent Blindness.

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Science
Volume 308Issue 572015 April 2005
Pages: 421 - 424

History

Received: 25 January 2005
Accepted: 22 February 2005

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Authors

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Albert O. Edwards*,
Department of Ophthalmology and McDermott Center for Human Growth and Development, University of Texas Southwestern Medical Center (UTSWMC), 5323 Harry Hines Boulevard, Dallas, TX 75390, USA.
Robert Ritter, III
Department of Ophthalmology and McDermott Center for Human Growth and Development, University of Texas Southwestern Medical Center (UTSWMC), 5323 Harry Hines Boulevard, Dallas, TX 75390, USA.
Kenneth J. Abel
Sequenom, Incorporated, 3595 John Hopkins Court, San Diego, CA 92121, USA.
Alisa Manning
Department of Medicine (Genetics Program), Boston University School of Medicine, 715 Albany Street, Boston, MA 02118, USA.
Carolien Panhuysen
Department of Medicine (Genetics Program), Boston University School of Medicine, 715 Albany Street, Boston, MA 02118, USA.
Department of Biostatistics, Boston University School of Public Health, 715 Albany Street, Boston, MA 02118, USA.
Lindsay A. Farrer
Department of Medicine (Genetics Program), Boston University School of Medicine, 715 Albany Street, Boston, MA 02118, USA.
Department of Neurology, Boston University School of Medicine, 715 Albany Street, Boston, MA 02118, USA.
Department of Genetics and Genomics, Boston University School of Medicine, 715 Albany Street, Boston, MA 02118, USA.
Department of Biostatistics, Boston University School of Public Health, 715 Albany Street, Boston, MA 02118, USA.
Department of Epidemiology, Boston University School of Public Health, 715 Albany Street, Boston, MA 02118, USA.

Notes

* To whom correspondence should be addressed. E-mail: [email protected]

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15 April 2005
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Received:25 January 2005
Accepted:22 February 2005
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