The DOI matches its Crossref record; 26 of the 27 references it cites were found in a registry or an index.
Discovery of Rare Variants via Sequencing: Implications for the Design of Complex Trait Association Studies
Open accessAbstract
There is strong evidence that rare variants are involved in complex disease etiology. The first step in implicating rare variants in disease etiology is their identification through sequencing in both randomly ascertained samples (e.g., the 1,000 Genomes Project) and samples ascertained according to disease status. We investigated to what extent rare variants will be observed across the genome and in candidate genes in randomly ascertained samples, the magnitude of variant enrichment in diseased individuals, and biases that can occur due to how variants are discovered. Although sequencing cases can enrich for casual variants, when a gene or genes are not involved in disease etiology, limiting variant discovery to cases can lead to association studies with dramatically inflated false positive rates.
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“The practice of identifying and quantifying allele frequencies in a group of individuals and comparing them with historical or publicly available ‘control’ sets in studies involving rare variants is highly problematic due to the potential for stratification and sampling variation effects.96”
From Statistical analysis strategies for association studies involving rare variants (2010) · cites this paper as [96]
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Metadata
- Authors
- Li, B., & Leal, S. M.
- Affiliations
- Baylor College of Medicine (US)
- Corresponding author
- Leal, Suzanne M.
- Venue
- PLoS Genetics
- Publisher
- Public Library of Science (PLoS)
- Published
- 2009-05-15
- Volume
- 5
- Issue
- 5
- Pages
- e1000481
- ISSN
- 1553-7390 (ISSN-L)
- 1553-7404
- PMC
- PMC2674213
- OpenAlex
- W2108409892
- Cited by
- 142
- References
- 27
- Citations by year
- 2025: 1 · 2024: 1 · 2023: 1 · 2021: 1 · 2020: 2 · 2019: 5 · 2018: 2 · 2017: 3 · 2016: 7 · 2015: 14 · 2014: 12 · 2013: 16 · 2012: 23
- FWCI
- 14.93
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS Genetics (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institutes of Health (R01-DC03594, DC03594)
- National Institute on Deafness and Other Communication Disorders (R01-DC03594, R01DC003594)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomics and Rare Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Forensic and Genetic Research
- Keywords
- rare variants, candidate genes, etiology, 1000 Genomes Project, causal variants
- MeSH terms
- Chromosome Mapping, False Positive Reactions, Gene Frequency, Haplotypes, Humans, Genetic Linkage, Models, Genetic, Probability, Genetic Variation, Models, Statistical, Genome, Human, Sequence Analysis, DNA, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, Genome-Wide Association Study
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