title: Complement factor H variant increases the risk of age-related macular degeneration.
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.
authors.affiliation: Center for Human Genetics Research, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
authors.forename: Jonathan L
authors.initials: JL
authors.lastname: Haines
authors.forename: Michael A
authors.initials: MA
authors.lastname: Hauser
authors.forename: Silke
authors.initials: S
authors.lastname: Schmidt
authors.forename: William K
authors.initials: WK
authors.lastname: Scott
authors.forename: Lana M
authors.initials: LM
authors.lastname: Olson
authors.forename: Paul
authors.initials: P
authors.lastname: Gallins
authors.forename: Kylee L
authors.initials: KL
authors.lastname: Spencer
authors.forename: Shu Ying
authors.initials: SY
authors.lastname: Kwan
authors.forename: Maher
authors.initials: M
authors.lastname: Noureddine
authors.forename: John R
authors.initials: JR
authors.lastname: Gilbert
authors.forename: Nathalie
authors.initials: N
authors.lastname: Schnetz-Boutaud
authors.forename: Anita
authors.initials: A
authors.lastname: Agarwal
authors.forename: Eric A
authors.initials: EA
authors.lastname: Postel
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Pericak-Vance
mesh_terms: D000368:Aged; D000483:Alleles; D001665:Binding Sites; D002097:C-Reactive Protein / Q000378:metabolism; D016022:Case-Control Studies; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D003167:Complement Activation; D017242:Complement Factor H / Q000032:analysis / Q000235:genetics* / Q000502:physiology; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006239:Haplotypes; D006493:Heparin / Q000378:metabolism; D006801:Humans; D015810:Linkage Disequilibrium; D008268:Macular Degeneration / Q000235:genetics*; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D017422:Sequence Analysis, DNA; D012907:Smoking
chemical_list: C493495:CFH protein, human; D017242:Complement Factor H; D006493:Heparin; D002097:C-Reactive Protein