Abstract
Age-related macular degeneration (AMD) is a leading cause of visual impairment and blindness in the elderly whose etiology remains largely unknown. Previous studies identified chromosome 1q32 as harboring a susceptibility locus for AMD. We used single-nucleotide polymorphisms to interrogate this region and identified a strongly associated haplotype in two independent data sets. DNA resequencing of the complement factor H gene within this haplotype revealed a common coding variant, Y402H, that significantly increases the risk for AMD with odds ratios between 2.45 and 5.57. This common variant likely explains approximately 43% of AMD in older adults.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Aged
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Alleles
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Binding Sites
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C-Reactive Protein / metabolism
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Case-Control Studies
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Chromosomes, Human, Pair 1 / genetics
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Complement Activation
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Complement Factor H / analysis
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Complement Factor H / genetics*
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Complement Factor H / physiology
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Gene Frequency
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Genetic Predisposition to Disease
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Genetic Variation*
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Genotype
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Haplotypes
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Heparin / metabolism
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Humans
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Linkage Disequilibrium
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Macular Degeneration / genetics*
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Odds Ratio
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Polymorphism, Single Nucleotide*
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Risk Factors
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Sequence Analysis, DNA
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Smoking
Substances
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CFH protein, human
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Complement Factor H
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Heparin
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C-Reactive Protein