Human Molecular Genetics Advance Access originally published online on June 29, 2005
Human Molecular Genetics 2005 14(15):2257-2264; doi:10.1093/hmg/ddi230
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Meta-analysis of genome scans of age-related macular degeneration
1Department of Medical and Molecular Genetics, Guy's, King's and St Thomas' School of Medicine, King's College London, London SE1 9RT, UK, 2Department of Biostatistics, 3 Department of Ophthalmology and Visual Sciences and 4Department of Human Genetics, University of Michigan, Ann Arbor, MI, USA, 5Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, OH, USA, 6Department of Ophthalmology and Visual Sciences, University of Wisconsin Medical School, Madison, WI, USA, 7Laboratory of Statistical Genetics, Rockefeller University, New York, NY, USA, 8Department of Ophthalmology, Macular Degeneration Center, Casey Eye Institute, Oregon Health and Science University, Portland, OR, USA, 9Harvard Medical School, Harvard School of Public Health, Boston, MA, USA, 10Ophthalmology/Epidemiology Unit, Massachusetts Eye and Ear Infirmary, Boston, MA, USA, 11Psychiatric and Neurodevelopmental Genetics Unit, Department of Psychiatry, Massachusetts General Hospital, Charlestown, MA, USA, 12Department of Human Genetics and 13Department of Biostatistics, University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA, USA, 14University of Pittsburgh School of Nursing and 15Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA, 16Department of Medicine, Center for Human Genetics, Duke University Medical Center, Durham, NC, USA, 17Center for Human Genetics Research, Vanderbilt University Medical Center, Nashville, TN, USA, 18Institute of Human Genetics, Biocenter, University of Wuerzburg, Wuerzburg, Germany and 19Institute of Human Genetics, University of Regensburg, Regensburg, Germany
* To whom correspondence should be addressed at: Department of Medical and Molecular Genetics, Guy's, King's and St Thomas' School of Medicine, King's College London, 8th Floor, Guy's Tower, Guy's Hospital, London SE1 9RT, UK. Tel: +44 2071883712; Fax: +44 2071882585; Email: sheila.fisher{at}genetics.kcl.ac.uk
Received April 7, 2005; Revised May 31, 2005; Accepted June 23, 2005
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 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.
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