Abstract
Age-related macular degeneration (AMD) is a major cause of blindness in the elderly. We report a genome-wide screen of 96 cases and 50 controls for polymorphisms associated with AMD. Among 116,204 single-nucleotide polymorphisms genotyped, an intronic and common variant in the complement factor H gene (CFH) is strongly associated with AMD (nominal P value <10(-7)). In individuals homozygous for the risk allele, the likelihood of AMD is increased by a factor of 7.4 (95% confidence interval 2.9 to 19). Resequencing revealed a polymorphism in linkage disequilibrium with the risk allele representing a tyrosine-histidine change at amino acid 402. This polymorphism is in a region of CFH that binds heparin and C-reactive protein. The CFH gene is located on chromosome 1 in a region repeatedly linked to AMD in family-based studies.
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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Aged, 80 and over
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Aging
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Alleles
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Amino Acid Substitution
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Case-Control Studies
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Choroid / immunology
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Chromosomes, Human, Pair 1 / genetics
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Complement Factor H / chemistry
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Complement Factor H / genetics*
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Complement Factor H / physiology
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Complement Membrane Attack Complex / analysis
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Exons
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Female
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Genetic Markers
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Genetic Predisposition to Disease
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Genotype
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Haplotypes
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Histidine / genetics
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Humans
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Immunity, Innate
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Introns
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Linkage Disequilibrium
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Macular Degeneration / genetics*
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Male
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Oligonucleotide Array Sequence Analysis
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Pigment Epithelium of Eye / immunology
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Polymorphism, Genetic
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Polymorphism, Single Nucleotide*
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Risk Factors
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Smoking
Substances
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CFH protein, human
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Complement Membrane Attack Complex
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Genetic Markers
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Histidine
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Complement Factor H