Meta-analysis of genome scans of age-related macular degeneration.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Fisher, SA; Abecasis, GR; Yashar, BM; Zareparsi, S; Swaroop, A; Iyengar, SK; Klein, BEK; Klein, R; Lee, KE; Majewski, J; Schultz, DW; Klein, ML; Seddon, JM; Santangelo, SL; Weeks, DE; Conley, YP; Mah, TS; Schmidt, S; Haines, JL; Pericak-Vance, MA; Gorin, MB; Schulz, HL; Pardi, F; Lewis, CM; Weber, BHF

Published Date

  • August 1, 2005

Published In

Volume / Issue

  • 14 / 15

Start / End Page

  • 2257 - 2264

PubMed ID

  • 15987700

Pubmed Central ID

  • 15987700

International Standard Serial Number (ISSN)

  • 0964-6906

Digital Object Identifier (DOI)

  • 10.1093/hmg/ddi230

Language

  • eng

Conference Location

  • England