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

3906 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
Externally published	Yes

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10.1126/science.1109557

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@article{13ab1bd82c9d44b782d07320d36a3afd,

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",

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

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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 - https://www.scopus.com/pages/publications/20244380171

UR - https://www.scopus.com/pages/publications/20244380171#tab=citedBy

U2 - 10.1126/science.1109557

DO - 10.1126/science.1109557

M3 - Article

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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

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