Meta-analysis of genome scans of age-related macular degeneration
Open accessAbstract
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.
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The most replicated linkage and association signals for AMD reside on chromosomes 1q25-31 and 10q26.
“Many linkage and association studies have indicated that the most replicated signals reside on chromosome 1q25–31 and 10q26 (Fisher et al., 2005; Jakobsdottir et al., 2005; Klein et al., 1998; Majewski et al., 2003).”
From Molecular pathology of age-related macular degeneration (2009) · cites this paper as Fisher et al., 2005
The finding of an AMD susceptibility locus on chromosome 10q26 has been replicated by other genome-wide linkage studies and supported by a genome-scan meta-analysis.
“This finding of an AMD susceptibility locus on chromosome 10q26 has been replicated by other genome-wide linkage studies (Weeks et al., 2004) and supported by a genome-scan meta-analysis (Fisher et al., 2005).”
From Molecular pathology of age-related macular degeneration (2009) · cites this paper as Fisher et al., 2005
In AMD, several independent studies and a meta-analysis of multiple genome scans suggested susceptibility loci with large effect at chromosomes 1q31 and 10q26.
“In AMD, several independent studies, and a meta-analysis of multiple genome scans (47), suggested susceptibility loci with large effect at chromosomes 1q31 and 10q26.”
From Unraveling a Multifactorial Late-Onset Disease: From Genetic Susceptibility to Disease Mechanisms for Age-Related Macular Degeneration (2009) · cites this paper as [47]
Analysis of a cohort of AMD patients with the human ortholog of MDM1 on chromosome 12q did not reveal an association between MDM1 and AMD.
“Analysis of a cohort of AMD patients with the human ortholog of MDM1 on chromosome 12q did not reveal an association between MDM1 and AMD”
From Retinal ultrastructure of murine models of dry age-related macular degeneration (AMD) (2010) · cites this paper as Fisher et al., 2005
The location of MDM1 on chromosome 12q has previously been reported to be an AMD susceptibility locus.
“though this location has previously been reported to be an AMD susceptibility locus”
From Retinal ultrastructure of murine models of dry age-related macular degeneration (AMD) (2010) · cites this paper as Fisher et al., 2005
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“Many linkage and association studies have indicated that the most replicated signals reside on chromosome 1q25–31 and 10q26 (Fisher et al., 2005; Jakobsdottir et al., 2005; Klein et al., 1998; Majewski et al., 2003).”
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Self-citation
- Authors
- Fisher, S. A., Abecasis, G. R., Yashar, B. M., Zareparsi, S., Swaroop, A., Iyengar, S. K., Klein, B. E. K., Klein, R., Lee, K. E., Majewski, J., Schultz, D. W., Klein, M. L., Seddon, J. M., Santangelo, S. L., Weeks, D. E., Conley, Y. P., Mah, T. S., Schmidt, S., Haines, J. L., Pericak-Vance, M. A., Gorin, M. B., Schulz, H. L., Pardi, F., Lewis, C. M., & Weber, B. H. F.
- Affiliations
- King's College London (GB)
- University of Michigan (US)
- Case Western Reserve University (US)
- University of Wisconsin–Madison (US)
- Rockefeller University (US)
- Oregon Health & Science University (US)
- Harvard University (US)
- University of Pittsburgh (US)
- Duke University (US)
- Vanderbilt University (US)
- University of Würzburg (DE)
- ORCID
- Venue
- Human Molecular Genetics
- Publisher
- Oxford University Press (OUP)
- Published
- 2005-06-29
- Volume
- 14
- Issue
- 15
- Pages
- 2257-2264
- ISSN
- 0964-6906 (ISSN-L)
- 1460-2083
- OpenAlex
- W2099907766
- Cited by
- 239
- References
- 55
- Citations by year
- 2025: 2 · 2024: 3 · 2023: 5 · 2022: 9 · 2021: 10 · 2020: 5 · 2019: 3 · 2018: 3 · 2017: 9 · 2016: 10 · 2015: 5 · 2014: 16 · 2013: 10 · 2012: 15
- FWCI
- 2.76
- Type
- journal article
- Language
- en
- Open access
- green
- www.escholarship.org
- Locations
- Human Molecular Genetics (publishedVersion)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- University of Regensburg Publication Server (University of Regensburg) (submittedVersion)
- Research Portal (King's College London) (submittedVersion)
- Funders
- Research to Prevent Blindness (EY06594)
- Collins Medical Trust
- Vanderbilt University
- Massachusetts Eye and Ear
- Massachusetts Lions Eye Research Fund
- Deutsche Forschungsgemeinschaft
- National Institutes of Health (EY10572, EY 06594)
- National Institute on Aging (AG-11268, P60AG011268)
- National Heart, Lung, and Blood Institute (HL07567, T32HL007567)
- National Human Genome Research Institute (HG 00008)
- National Eye Institute (R01EY008247, EY 03279, R01-U10-EY06594, EY12562, EY 012203, R01EY012562, U10EY011309, R01EY012203, EY 08247, EY-10572, U10EY006594, R03EY015216, R01EY003279, R01EY009859, EY10605, EY015216, EY11309, R01EY010605, F32EY014085, R01EY011309, EY015288, EY12118, P30EY010572)
- National Institute of General Medical Sciences (GM-28356)
- National Center for Research Resources (RR-03655, M01RR000095, P41RR003655)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinal Development and Disorders
- Keywords
- age-related macular degeneration, genetic susceptibility loci, genome-wide linkage analysis, chromosome 10q26, candidate gene association, genetic epidemiology
- MeSH terms
- Aging, Humans, Genetic Linkage, Macular Degeneration, Genome, Human, Genetic Predisposition to Disease
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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