Purchase this article with an account.
B.H. F. Weber, S.A. Fisher, C.M. Lewis, AMD Genome Search Meta–Analysis Study Group; Meta–Analysis of AMD Genome Scans Confirms a Susceptibility Locus on Chromosome 10q . Invest. Ophthalmol. Vis. Sci. 2005;46(13):3203.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Purpose: A genetic contribution to AMD susceptibility is well established. Several genome–wide linkage studies have been carried out in AMD with the most widely replicated regions of linkage on chromosomes 1q and 10q. However, several other regions exhibiting significant linkage in individual studies show only anecdotal evidence for replication across studies. The genome scan meta–analysis (GSMA) method 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. Methods: Six AMD genome scans (Abecasis et al, 2004; Iyengar et al, 2004, Majewski et al, 2003; Schick et al, 2003; Seddon et al, 2003; Weeks et al, 2004) were identified for inclusion and primary investigators of each study were invited to contribute genome–wide linkage results. 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 ∼30cM 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. Results: The strongest evidence for an AMD susceptibility locus was found on chromosome 10q26 where genome–wide significant linkage was observed (p=0.00025); an adjacent bin showed suggestive evidence for linkage. This region has shown nominal linkage (p<0.01) in 4 of the 6 linkage studies. 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. Conclusions: Several of the regions identified in this analysis showed only weak evidence for linkage in individual studies. These results will help prioritise regions for future positional and functional candidate gene studies in AMD.
This PDF is available to Subscribers Only