Genetics of pigment changes and geographic atrophy.
OBJECTIVE
Studies of age-related macular degeneration (AMD) often involve persons with both choroidal neovascularization and geographic atrophy (GA), but few genome-wide scans (GWSs) have discriminated between these two outcomes.


METHODS
To comprehend the role of pigmentary abnormalities (PA) and GA in AMD, the authors analyzed the data from a previous GWS on AMD (FARMS [Family Age-Related Maculopathy Study]sample of 34 extended families) looking only at PA. Presented are new GWS data from the full Beaver Dam Eye Study (BDES) family cohort, including longitudinal data at baseline and 5- and 10-year follow-up. A linkage analysis for PA/GA was performed on both samples for 338 markers covering all autosomes. Another linkage analysis using the rate of change along the PA/GA scale was performed with the BDES sample.


RESULTS
Analysis of the FARMS sample provided evidence for linkage with P < 0.01 in the 1q25, 5p13, 6q21-23, and 11q14 regions. The most significant peak was found on chromosome 1, near complement factor H (CFH), with P= 6.20 x 10(-4). Analysis using the rate of change in BDES replicated the peaks in 5p13 and 6q21-23, suggesting that these loci may contribute to the rate of progression of PA/GA. Association analysis of CFH polymorphisms suggest that CFH may play a role in the development of pigmentary abnormalities and may modify the progression along the PA/GA scale.


CONCLUSIONS
These findings suggest a complex, heterogeneous model for PA/GA.
Thompson
Cheryl L
CL
Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, Ohio 44106-7281, USA.
Jun
Gyungah
G
Klein
Barbara E K
BE
Klein
Ronald
R
Capriotti
Jennifer
J
Lee
Kristine E
KE
Iyengar
Sudha K
SK
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001284:Atrophy; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics*; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics*; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics*; D008040:Genetic Linkage; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D015894:Genome, Human; D005838:Genotype; D006801:Humans; D008268:Macular Degeneration / Q000235:genetics*; D008875:Middle Aged; D010641:Phenotype; D010857:Pigment Epithelium of Eye / Q000473:pathology*
D005819:Genetic Markers