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

Sheila A. Fisher, Goncalo R. Abecasis, Beverly M. Yashar, Sepideh Zareparsi, Anand Swaroop, Sudha K. Iyengar, Barbara E K Klein, Ronald Klein, Kristine E. Lee, Jacek Majewski, Dennis W. Schultz, Michael Klein, Johanna M. Seddon, Susan L. Santangelo, Daniel E. Weeks, Yvette P. Conley, Tammy S. Mah, Silke Schmidt, Jonathan L. Haines, Margaret A. Pericak-Vance & 5 others Michael B. Gorin, Heidi L. Schulz, Fabio Pardi, Cathryn M. Lewis, Bernhard H F Weber

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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.

Original languageEnglish (US)
Pages (from-to)2257-2264
Number of pages8
JournalHuman Molecular Genetics
Volume14
Issue number15
DOIs
StatePublished - Aug 1 2005

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Macular Degeneration
Meta-Analysis
Genome
Chromosomes
Phenotype
Genes

ASJC Scopus subject areas

  • Genetics

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Fisher, S. A., Abecasis, G. R., Yashar, B. M., Zareparsi, S., Swaroop, A., Iyengar, S. K., ... Weber, B. H. F. (2005). Meta-analysis of genome scans of age-related macular degeneration. Human Molecular Genetics, 14(15), 2257-2264. https://doi.org/10.1093/hmg/ddi230

Meta-analysis of genome scans of age-related macular degeneration. / Fisher, Sheila A.; Abecasis, Goncalo R.; Yashar, Beverly M.; Zareparsi, Sepideh; Swaroop, Anand; Iyengar, Sudha K.; Klein, Barbara E K; Klein, Ronald; Lee, Kristine E.; Majewski, Jacek; Schultz, Dennis W.; Klein, Michael; Seddon, Johanna M.; Santangelo, Susan L.; Weeks, Daniel E.; Conley, Yvette P.; Mah, Tammy S.; Schmidt, Silke; Haines, Jonathan L.; Pericak-Vance, Margaret A.; Gorin, Michael B.; Schulz, Heidi L.; Pardi, Fabio; Lewis, Cathryn M.; Weber, Bernhard H F.

In: Human Molecular Genetics, Vol. 14, No. 15, 01.08.2005, p. 2257-2264.

Research output: Contribution to journalArticle

Fisher, SA, Abecasis, GR, Yashar, BM, Zareparsi, S, Swaroop, A, Iyengar, SK, Klein, BEK, Klein, R, Lee, KE, Majewski, J, Schultz, DW, Klein, M, 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 2005, 'Meta-analysis of genome scans of age-related macular degeneration', Human Molecular Genetics, vol. 14, no. 15, pp. 2257-2264. https://doi.org/10.1093/hmg/ddi230
Fisher SA, Abecasis GR, Yashar BM, Zareparsi S, Swaroop A, Iyengar SK et al. Meta-analysis of genome scans of age-related macular degeneration. Human Molecular Genetics. 2005 Aug 1;14(15):2257-2264. https://doi.org/10.1093/hmg/ddi230
Fisher, Sheila A. ; Abecasis, Goncalo R. ; Yashar, Beverly M. ; Zareparsi, Sepideh ; Swaroop, Anand ; Iyengar, Sudha K. ; Klein, Barbara E K ; Klein, Ronald ; Lee, Kristine E. ; Majewski, Jacek ; Schultz, Dennis W. ; Klein, Michael ; Seddon, Johanna M. ; Santangelo, Susan L. ; Weeks, Daniel E. ; Conley, Yvette P. ; Mah, Tammy S. ; Schmidt, Silke ; Haines, Jonathan L. ; Pericak-Vance, Margaret A. ; Gorin, Michael B. ; Schulz, Heidi L. ; Pardi, Fabio ; Lewis, Cathryn M. ; Weber, Bernhard H F. / Meta-analysis of genome scans of age-related macular degeneration. In: Human Molecular Genetics. 2005 ; Vol. 14, No. 15. pp. 2257-2264.
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AU - Swaroop, Anand

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AU - Lee, Kristine E.

AU - Majewski, Jacek

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AU - Seddon, Johanna M.

AU - Santangelo, Susan L.

AU - Weeks, Daniel E.

AU - Conley, Yvette P.

AU - Mah, Tammy S.

AU - Schmidt, Silke

AU - Haines, Jonathan L.

AU - Pericak-Vance, Margaret A.

AU - Gorin, Michael B.

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AU - Pardi, Fabio

AU - Lewis, Cathryn M.

AU - Weber, Bernhard H F

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