Complement factor H variant increases the risk of age-related macular degeneration.
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.
Haines
Jonathan L
JL
Center for Human Genetics Research, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Hauser
Michael A
MA
Schmidt
Silke
S
Scott
William K
WK
Olson
Lana M
LM
Gallins
Paul
P
Spencer
Kylee L
KL
Kwan
Shu Ying
SY
Noureddine
Maher
M
Gilbert
John R
JR
Schnetz-Boutaud
Nathalie
N
Agarwal
Anita
A
Postel
Eric A
EA
Pericak-Vance
Margaret A
MA
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
C493495:CFH protein, human; D017242:Complement Factor H; D006493:Heparin; D002097:C-Reactive Protein