Cited by 1,198Genetic Associations and EpidemiologyForensic and Genetic ResearchGenetic diversity and population structure

Use of Unlinked Genetic Markers to Detect Population Stratification in Association Studies

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Pritchard, Jonathan K., Rosenberg, Noah A.·1999·The American Journal of Human Genetics

Abstract

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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Crossref · 10.1086/302449

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26 of 26 references verified0 citation errors · 0 not checkable

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  • Methods were developed to detect and adjust for ancestry biases and unexpected relatedness between subjects.

    “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]

  • Under the null (one-cluster) model of no population structure, there was a large excess of small P values in χ2 tests for association with skin color, and a global test for population stratification based on the sum of χ2 statistics was highly statistically significant (P < 10^-40).

    “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”

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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)
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
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

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