Complement factor H polymorphism in age-related macular degeneration

Robert J. Klein; Caroline Zeiss; Emily Y. Chew; Jen Yue Tsai; Richard S. Sackler; Chad Haynes; Alice K. Henning; John Paul SanGiovanni; Shrikant M. Mane; Susan T. Mayne; Michael B. Bracken; Frederick L. Ferris; Jurg Ott; Colin Barnstable; Josephine Hoh

doi:10.1126/science.1109557

Complement factor H polymorphism in age-related macular degeneration

Robert J. Klein, Caroline Zeiss, Emily Y. Chew, Jen Yue Tsai, Richard S. Sackler, Chad Haynes, Alice K. Henning, John Paul SanGiovanni, Shrikant M. Mane, Susan T. Mayne, Michael B. Bracken, Frederick L. Ferris, Jurg Ott, Colin Barnstable, Josephine Hoh

Research output: Contribution to journal › Article › peer-review

3801 Scopus citations

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.

Original language	English (US)
Pages (from-to)	385-389
Number of pages	5
Journal	Science
Volume	308
Issue number	5720
DOIs	https://doi.org/10.1126/science.1109557
State	Published - Apr 15 2005

All Science Journal Classification (ASJC) codes

General

Access to Document

10.1126/science.1109557

Cite this

@article{33d7ae09434043d392c8ed86e59673f5,

title = "Complement factor H polymorphism in age-related macular degeneration",

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.",

author = "Klein, {Robert J.} and Caroline Zeiss and Chew, {Emily Y.} and Tsai, {Jen Yue} and Sackler, {Richard S.} and Chad Haynes and Henning, {Alice K.} and SanGiovanni, {John Paul} and Mane, {Shrikant M.} and Mayne, {Susan T.} and Bracken, {Michael B.} and Ferris, {Frederick L.} and Jurg Ott and Colin Barnstable and Josephine Hoh",

year = "2005",

month = apr,

day = "15",

doi = "10.1126/science.1109557",

language = "English (US)",

volume = "308",

pages = "385--389",

journal = "Science",

issn = "0036-8075",

publisher = "American Association for the Advancement of Science",

number = "5720",

}

TY - JOUR

T1 - Complement factor H polymorphism in age-related macular degeneration

AU - Klein, Robert J.

AU - Zeiss, Caroline

AU - Chew, Emily Y.

AU - Tsai, Jen Yue

AU - Sackler, Richard S.

AU - Haynes, Chad

AU - Henning, Alice K.

AU - SanGiovanni, John Paul

AU - Mane, Shrikant M.

AU - Mayne, Susan T.

AU - Bracken, Michael B.

AU - Ferris, Frederick L.

AU - Ott, Jurg

AU - Barnstable, Colin

AU - Hoh, Josephine

PY - 2005/4/15

Y1 - 2005/4/15

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=20244380171&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=20244380171&partnerID=8YFLogxK

U2 - 10.1126/science.1109557

DO - 10.1126/science.1109557

M3 - Article

C2 - 15761122

AN - SCOPUS:20244380171

SN - 0036-8075

VL - 308

SP - 385

EP - 389

JO - Science

JF - Science

IS - 5720

ER -

Complement factor H polymorphism in age-related macular degeneration

Abstract

All Science Journal Classification (ASJC) codes

Access to Document

Other files and links

Fingerprint

Cite this