Genetic profile for five common variants associated with age-related macular degeneration in densely affected families: a novel analytic approach
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About 40% of the genetic variance of age-related macular degeneration (AMD) can be explained by a common variation at five common single-nucleotide polymorphisms (SNPs). We evaluated the degree to which these known variants explain the clustering of AMD in a group of densely affected families. We sought to determine whether the actual number of risk alleles at the five variants in densely affected families matched the expected number. Using data from 322 families with AMD, we used a simulation strategy to generate comparison groups of families and determined whether their genetic profile at the known AMD risk loci differed from the observed genetic profile, given the density of disease observed. Overall, the genotypic loads for the five SNPs in the families did not deviate significantly from the genotypic loads predicted by the simulation. However, for a subset of densely affected families, the mean genotypic load in the families was significantly lower than the expected load determined from the simulation. Given that these densely affected families may harbor rare, more penetrant variants for AMD, linkage analyses and resequencing targeting these families may be an effective approach to finding additional implicated genes.
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The genetic variants known to date are estimated to account for <50% of the heritability of AMD.
“The genetic variants known to date are estimated to account for <50% of the heritability of the disease (8,20).”
From Common variants near FRK/COL10A1 and VEGFA are associated with advanced age-related macular degeneration (2011) · cites this paper as [20]
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“The genetic variants known to date are estimated to account for ,50% of the heritability of the disease (8,20).”
BackgroundSelf-citationGenetics and genetic testing for age-related macular degeneration
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- Authors
- Sobrin, L., Maller, J. B., Neale, B. M., Reynolds, R. C., Fagerness, J. A., Daly, M. J., & Seddon, J. M.
- Affiliations
- Massachusetts Eye and Ear Infirmary (US)
- Broad Institute (US)
- Tufts Medical Center (US)
- Tufts University (US)
- Corresponding author
- Seddon, Johanna M
- Venue
- European Journal of Human Genetics
- Published
- 2009-10-21
- Volume
- 18
- Issue
- 4
- Pages
- 496-501
- ISSN
- 1018-4813 (ISSN-L)
- 1476-5438
- PMC
- PMC2911949
- OpenAlex
- W1967207909
- Cited by
- 31
- References
- 19
- Citations by year
- 2024: 1 · 2022: 1 · 2021: 2 · 2019: 1 · 2018: 1 · 2017: 2 · 2016: 2 · 2015: 1 · 2014: 5 · 2013: 5 · 2012: 6
- FWCI
- 3.39
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- European Journal of Human Genetics (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Foundation Fighting Blindness
- Tufts Medical Center
- Broad Institute
- National Institutes of Health (5k12ey016335-17, 6u54rr020278-06)
- National Eye Institute (U10EY011309, EY16335-02, K12-EY016335, EY11309, R01EY011309)
- National Center for Research Resources (U54-RR020278)
- Topics
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinal Development and Disorders
- Keywords
- age-related macular degeneration, single nucleotide polymorphisms, genetic risk variants, familial aggregation, rare variants, penetrance, linkage analysis, resequencing
- MeSH terms
- Computer Simulation, Family, Female, Genetic Testing, Genotype, Humans, Genetic Linkage, Macular Degeneration, Male, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, Genome-Wide Association Study
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