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Use of Unlinked Genetic Markers to Detect Population Stratification in Association Studies
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We examine the issue of population stratification in association-mapping studies. In case-control studies of association, population subdivision or recent admixture of populations can lead to spurious associations between a phenotype and unlinked candidate loci. Using a model of sampling from a structured population, we show that if population stratification exists, it can be detected by use of unlinked marker loci. We show that the case-control-study design, using unrelated control individuals, is a valid approach for association mapping, provided that marker loci unlinked to the candidate locus are included in the study, to test for stratification. We suggest guidelines as to the number of unlinked marker loci to use.
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“Methods were developed to detect and adjust for such biases (67–69) as well as unexpected relatedness between subjects.”
From Genetic Mapping in Human Disease (2008) · cites this paper as [68]
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“Under the null (one-cluster) model of no population structure, for which the L and H groups are assumed to be well matched, we observed a large excess of small P values in x 2 tests for association with skin color (table 2), and a global test for population stratification based on the sum of x 2 statistics 46 was highly statistically significant”
From A Genomewide Association Study of Skin Pigmentation in a South Asian Population (2007) · cites this paper as [46]
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Metadata
- Authors
- Pritchard, J. K., & Rosenberg, N. A.
- Affiliations
- University of Oxford (GB)
- Stanford University (US)
- Corresponding author
- Pritchard, Jonathan K.
- Venue
- The American Journal of Human Genetics
- Publisher
- Elsevier BV
- Published
- 1999-07
- Volume
- 65
- Issue
- 1
- Pages
- 220-228
- ISSN
- 0002-9297 (ISSN-L)
- PMC
- PMC1378093
- OpenAlex
- W2116329478
- Cited by
- 1,198
- References
- 27
- Citations by year
- 2026: 9 · 2025: 3 · 2024: 9 · 2023: 6 · 2022: 3 · 2021: 9 · 2020: 13 · 2019: 49 · 2018: 21 · 2017: 12 · 2016: 22 · 2015: 27 · 2014: 28 · 2013: 42 · 2012: 46
- FWCI
- 27.14
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- The American Journal of Human Genetics (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Defense Science and Engineering Graduate
- National Institute of General Medical Sciences (GM19634, GM 28428, F32GM019634, P01GM028428)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Forensic and Genetic Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic diversity and population structure
- Keywords
- population stratification, association mapping, case-control study, spurious association, admixture, population structure
- MeSH terms
- Alleles, Genetic Markers, Genotype, Humans, Genetic Linkage, Models, Genetic, Research Design, Case-Control Studies
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.
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