Synthetic associations in the context of genome-wide association scan signals
Open accessAbstract
Genome-wide association studies (GWAS) have successfully identified a large number of genetic variants associated with complex traits, but these only explain a small proportion of the total heritability. It has been recently proposed that rare variants can create 'synthetic association' signals in GWAS, by occurring more often in association with one of the alleles of a common tag single nucleotide polymorphism. While the ultimate evaluation of this hypothesis will require the completion of large-scale sequencing studies, it is informative to place it in the broader context of what is known about the genetic architecture of complex disease. In this review, we draw from empirical and theoretical data to summarize evidence showing that synthetic associations do not underlie many reported GWAS associations.
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Polygenicity may be a general feature of complex biomedical diseases.
“Polygenicity may be a general feature of complex biomedical diseases. 128,129”
From Genetic architectures of psychiatric disorders: the emerging picture and its implications (2012) · cites this paper as [128]
It is possible to provide realistic estimates of power and to predict the number of new associations for each increment in sample size.
“It is possible to provide realistic estimates of power and to predict the number of new associations for each increment in sample size 128,129,140”
From Genetic architectures of psychiatric disorders: the emerging picture and its implications (2012) · cites this paper as [128]
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- Authors
- Orozco, G., Barrett, J. C., & Zeggini, E.
- Affiliations
- University of Manchester (GB)
- Wellcome Sanger Institute (GB)
- Corresponding author
- Zeggini, E.
- Venue
- Human Molecular Genetics
- Publisher
- Oxford University Press (OUP)
- Published
- 2010-08-30
- Volume
- 19
- Issue
- R2
- Pages
- R137-R144
- ISSN
- 0964-6906 (ISSN-L)
- 1460-2083
- PMC
- PMC2953742
- OpenAlex
- W2109003746
- Cited by
- 61
- References
- 75
- Citations by year
- 2026: 3 · 2024: 1 · 2022: 2 · 2021: 4 · 2019: 2 · 2018: 1 · 2017: 3 · 2016: 2 · 2015: 6 · 2014: 5 · 2013: 10 · 2012: 12
- FWCI
- 1.08
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- other-oa
- Locations
- Human Molecular Genetics (publishedVersion, other-oa)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Research Explorer (The University of Manchester) (submittedVersion)
- Funders
- Wellcome Trust (WT088885/Z/09/Z, WT089120/Z/09/Z)
- European Commission (235662)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Mapping and Diversity in Plants and Animals
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and phenotypic traits in livestock
- Keywords
- rare variants, missing heritability
- MeSH terms
- Humans, Genetic Variation, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, Genome-Wide Association Study
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