Meta-analysis of genome scans of age-related macular degeneration.
A genetic contribution to the development of age-related macular degeneration (AMD) is well established. Several genome-wide linkage studies have identified a number of putative susceptibility loci for AMD but only a few of these regions have been replicated in independent studies. Here, we perform a meta-analysis of six AMD genome screens using the genome-scan meta-analysis method, which allows linkage results from several studies to be combined, providing greater power to identify regions that show only weak evidence for linkage in individual studies. Results from non-parametric analysis for a broad AMD clinical phenotype (including two studies with quantitative traits) were extracted. For each study, 120 genomic bins of approximately 30 cM were defined and ranked according to maximum evidence for linkage within each bin. Bin ranks were weighted according to study size and summed across all studies; the summed rank (SR) for each bin was assessed empirically for significance using permutation methods. A high SR indicates a region with consistent evidence for linkage across studies. The strongest evidence for an AMD susceptibility locus was found on chromosome 10q26 where genome-wide significant linkage was observed (P=0.00025). Several other regions met the empirical significance criteria for bins likely to contain linked loci including adjacent pairs of bins on chromosomes 1q, 2p, 3p and 16. Several of the regions identified here showed only weak evidence for linkage in the individual studies. These results will help prioritize regions for future positional and functional candidate gene studies in AMD.
Fisher
Sheila A
SA
Department of Medical and Molecular Genetics, Guy's, King's and St Thomas' School of Medicine, King's College London, London SE1 9RT, UK. sheila.fisher@genetics.kcl.ac.uk
Abecasis
Goncalo R
GR
Yashar
Beverly M
BM
Zareparsi
Sepideh
S
Swaroop
Anand
A
Iyengar
Sudha K
SK
Klein
Barbara E K
BE
Klein
Ronald
R
Lee
Kristine E
KE
Majewski
Jacek
J
Schultz
Dennis W
DW
Klein
Michael L
ML
Seddon
Johanna M
JM
Santangelo
Susan L
SL
Weeks
Daniel E
DE
Conley
Yvette P
YP
Mah
Tammy S
TS
Schmidt
Silke
S
Haines
Jonathan L
JL
Pericak-Vance
Margaret A
MA
Gorin
Michael B
MB
Schulz
Heidi L
HL
Pardi
Fabio
F
Lewis
Cathryn M
CM
Weber
Bernhard H F
BH
D000375:Aging / Q000235:genetics; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D015894:Genome, Human; D006801:Humans; D008268:Macular Degeneration / Q000235:genetics*