@article{e89c57464bc046beb5c40c2cafdc30ce,
title = "Meta-analysis of genome scans of age-related macular degeneration",
abstract = "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 ∼30 14;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.",
author = "Fisher, {Sheila A.} and Abecasis, {Goncalo R.} and Yashar, {Beverly M.} and Sepideh Zareparsi and Anand Swaroop and Iyengar, {Sudha K.} and Klein, {Barbara E.K.} and Ronald Klein and Lee, {Kristine E.} and Jacek Majewski and Schultz, {Dennis W.} and Klein, {Michael L.} and Seddon, {Johanna M.} and Santangelo, {Susan L.} and Weeks, {Daniel E.} and Conley, {Yvette P.} and Mah, {Tammy S.} and Silke Schmidt and Haines, {Jonathan L.} and Pericak-Vance, {Margaret A.} and Gorin, {Michael B.} and Schulz, {Heidi L.} and Fabio Pardi and Lewis, {Cathryn M.} and Weber, {Bernhard H.F.}",
note = "Funding Information: This study was supported in part by grants from the National Institutes of Health (NIH) National Eye Institute: F32-EY014085 (S.Z.), EY015288 (B.E.K.K.), R01-EY10605 (B.E.K.K.), EY012203 (M.L.K.), R01-U10-EY06594 (R.K. and B.E.K.K.), EY03279 (J.M.), EY08247 (J.M.), EY10572 (J.M.), R01-EY11309 (J.M.S.), U10-EY11309 (J.M.S.), EY12562 (G.R.A.), U10-EY06594 (S.K.I.), EY10605 (S.K.I.), EY11309 (J.M.S.), EY015216 (S.S.), EY12118 (M.P.V. and J.L.H.), R01-EY 09859 (M.B.G.); National Institute of Aging: AG11268 (H Cohen); National Institute of General Medical Sciences: GM28356 (S.K.I.); National Center for Research Resources: RR03655 (S.K.I.), M01 RR-00095 (Vanderbilt University); National Human Genome Research Institute: HG00008 (J.M. and J Ott); Foundation Fighting Blindness (A.S., D.W.S. and J.M.S.); Research to Prevent Blindness (A.S., M.L.K., M.B.G., R.K., J.M. and J.M.S.); Macular Vision Research Foundation (A.S.); The Elmer and Sylvia Sramek Foundation (A.S.); The American Federation for Aging Research (A.S.); Smith Kettlewell Eye Research Foundation (M.B.G.); The Steinbach Foundation (M.B.G.); Pennsylvanian Lions Sight Conservation (M.B.G.); Massachusetts Eye Research Foundation (M.B.G.); National Heart, Lung and Blood Institute: HL07567 (S.K.I.); The Collins Medical Trust (J.M.); The George and Carolyn Goodall Macular Degeneration Fund (M.L.K.); Massachusetts Lions Eye Research Fund, Inc. (J.M.S.); Epidemiology Unit Fund, Massachusetts Eye and Ear Infirmary (J.M.S.) and the Deutsche Forschungsgemeinschaft: DFG WE 1259/14-3 (B.H.F.W.).",
year = "2005",
month = aug,
day = "1",
doi = "10.1093/hmg/ddi230",
language = "English (US)",
volume = "14",
pages = "2257--2264",
journal = "Human molecular genetics",
issn = "0964-6906",
publisher = "Oxford University Press",
number = "15",
}