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Originally published in Science Express on 19 October 2006
Science 10 November 2006:
Vol. 314. no. 5801, pp. 989 - 992
DOI: 10.1126/science.1133807
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Reports

HTRA1 Promoter Polymorphism in Wet Age-Related Macular Degeneration

Andrew DeWan,1 Mugen Liu,2* Stephen Hartman,3* Samuel Shao-Min Zhang,2* David T. L. Liu,4 Connie Zhao,5 Pancy O. S. Tam,4 Wai Man Chan,4 Dennis S. C. Lam,4 Michael Snyder,3 Colin Barnstable,2 Chi Pui Pang,4 Josephine Hoh1,2{dagger}

Age-related macular degeneration (AMD), the most common cause of irreversible vision loss in individuals aged older than 50 years, is classified as either wet (neovascular) or dry (nonneovascular). Inherited variation in the complement factor H gene is a major risk factor for drusen in dry AMD. Here we report that a single-nucleotide polymorphism in the promoter region of HTRA1, a serine protease gene on chromosome 10q26, is a major genetic risk factor for wet AMD. A whole-genome association mapping strategy was applied to a Chinese population, yielding a P value of <10–11. Individuals with the risk-associated genotype were estimated to have a likelihood of developing wet AMD 10 times that of individuals with the wild-type genotype.

1 Department of Epidemiology and Public Health, Yale University, 60 College Street, New Haven, CT 06520, USA.
2 Department of Ophthalmology and Visual Science, Yale University, 330 Cedar Street, New Haven, CT 06520, USA.
3 Department of Molecular, Cellular, and Developmental Biology, Yale University, 219 Prospect Street, New Haven, CT 06520, USA.
4 Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, China.
5 Genomics Resource Center, Rockefeller University, 1230 York Avenue, New York, NY 10021, USA.

* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: josephine.hoh{at}yale.edu

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