Complement Factor H Polymorphism in Age-Related Macular Degeneration

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 ge...

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Published in	Science (American Association for the Advancement of Science) Vol. 308; no. 5720; pp. 385 - 389
Main Authors	Klein, Robert J, Zeiss, Caroline, Chew, Emily Y, Tsai, Jen-Yue, Sackler, Richard S, Haynes, Chad, Henning, Alice K, SanGiovanni, John Paul, Mane, Shrikant M, Mayne, Susan T, Bracken, Michael B, Ferris, Frederick L, Ott, Jurg, Barnstable, Colin, Hoh, Josephine
Format	Journal Article
Language	English
Published	Washington, DC American Association for the Advancement of Science 15.04.2005 The American Association for the Advancement of Science
Subjects	Aged Aged, 80 and over Aging Alleles Amino Acid Substitution Amino acids Biological and medical sciences Blindness C-reactive protein Care and treatment Case-Control Studies Choroid - immunology Chromosomes Chromosomes, Human, Pair 1 - genetics complement Complement Factor H - chemistry Complement Factor H - genetics Complement Factor H - physiology Complement Membrane Attack Complex - analysis confidence interval Drusen elderly Exons Family studies Female Genes Genetic Markers Genetic Predisposition to Disease Genomes Genotype Genotype & phenotype Genotypes genotyping Haplotypes heparin Histidine - genetics homozygosity Humans Immunity, Innate Introns Linkage Disequilibrium Macular degeneration Macular Degeneration - genetics Magnetic fields Male Medical genetics Medical sciences Older people Oligonucleotide Array Sequence Analysis Ophthalmology P values Pigment Epithelium of Eye - immunology Polymorphism Polymorphism, Genetic Polymorphism, Single Nucleotide Proteins Retinopathies risk Risk Factors single nucleotide polymorphism Smoking Vision United States Macular degeneration Human Eye disease Retinopathy Complement Age Polymorphism
Online Access	Get full text
ISSN	0036-8075 1095-9203 1095-9203
DOI	10.1126/science.1109557

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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.
AbstractList	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.sup.-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. 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 10sup -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 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. 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. 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 super(-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. 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^sup -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 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. 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. 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.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.
Audience	Academic
Author	Barnstable, Colin SanGiovanni, John Paul Klein, Robert J Sackler, Richard S Mayne, Susan T Mane, Shrikant M Henning, Alice K Haynes, Chad Tsai, Jen-Yue Ott, Jurg Ferris, Frederick L Hoh, Josephine Chew, Emily Y Zeiss, Caroline Bracken, Michael B
Author_xml	– sequence: 1 fullname: Klein, Robert J – sequence: 2 fullname: Zeiss, Caroline – sequence: 3 fullname: Chew, Emily Y – sequence: 4 fullname: Tsai, Jen-Yue – sequence: 5 fullname: Sackler, Richard S – sequence: 6 fullname: Haynes, Chad – sequence: 7 fullname: Henning, Alice K – sequence: 8 fullname: SanGiovanni, John Paul – sequence: 9 fullname: Mane, Shrikant M – sequence: 10 fullname: Mayne, Susan T – sequence: 11 fullname: Bracken, Michael B – sequence: 12 fullname: Ferris, Frederick L – sequence: 13 fullname: Ott, Jurg – sequence: 14 fullname: Barnstable, Colin – sequence: 15 fullname: Hoh, Josephine
BackLink	http://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=16708209$$DView record in Pascal Francis https://www.ncbi.nlm.nih.gov/pubmed/15761122$$D View this record in MEDLINE/PubMed
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Snippet	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...
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SubjectTerms	Aged Aged, 80 and over Aging Alleles Amino Acid Substitution Amino acids Biological and medical sciences Blindness C-reactive protein Care and treatment Case-Control Studies Choroid - immunology Chromosomes Chromosomes, Human, Pair 1 - genetics complement Complement Factor H - chemistry Complement Factor H - genetics Complement Factor H - physiology Complement Membrane Attack Complex - analysis confidence interval Drusen elderly Exons Family studies Female Genes Genetic Markers Genetic Predisposition to Disease Genomes Genotype Genotype & phenotype Genotypes genotyping Haplotypes heparin Histidine - genetics homozygosity Humans Immunity, Innate Introns Linkage Disequilibrium Macular degeneration Macular Degeneration - genetics Magnetic fields Male Medical genetics Medical sciences Older people Oligonucleotide Array Sequence Analysis Ophthalmology P values Pigment Epithelium of Eye - immunology Polymorphism Polymorphism, Genetic Polymorphism, Single Nucleotide Proteins Retinopathies risk Risk Factors single nucleotide polymorphism Smoking Vision
Title	Complement Factor H Polymorphism in Age-Related Macular Degeneration
URI	https://www.jstor.org/stable/3841242 https://www.ncbi.nlm.nih.gov/pubmed/15761122 https://www.proquest.com/docview/213593179 https://www.proquest.com/docview/17777486 https://www.proquest.com/docview/46651048 https://www.proquest.com/docview/67748412 https://www.proquest.com/docview/743130250 https://pubmed.ncbi.nlm.nih.gov/PMC1512523
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