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Discerning the Ancestry of European Americans in Genetic Association Studies
Open accessAbstract
European Americans are often treated as a homogeneous group, but in fact form a structured population due to historical immigration of diverse source populations. Discerning the ancestry of European Americans genotyped in association studies is important in order to prevent false-positive or false-negative associations due to population stratification and to identify genetic variants whose contribution to disease risk differs across European ancestries. Here, we investigate empirical patterns of population structure in European Americans, analyzing 4,198 samples from four genome-wide association studies to show that components roughly corresponding to northwest European, southeast European, and Ashkenazi Jewish ancestry are the main sources of European American population structure. Building on this insight, we constructed a panel of 300 validated markers that are highly informative for distinguishing these ancestries. We demonstrate that this panel of markers can be used to correct for stratification in association studies that do not generate dense genotype data.
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“This false positive association between the LCT locus and skin pigmentation mirrors the false positive association found between the LCT locus and height [31], [32].”
From Genome-Wide Association Studies of Quantitatively Measured Skin, Hair, and Eye Pigmentation in Four European Populations (2012) · cites this paper as [32]
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“Previous studies have shown that more than 1,000 ancestry-informative markers are needed to derive the first two genetic PCs of European structure adequately representing the North/South and East/West axes of differentiation [32], [48].”
From Genome-Wide Association Studies of Quantitatively Measured Skin, Hair, and Eye Pigmentation in Four European Populations (2012) · cites this paper as [32]
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Metadata
- Authors
- Price, A. L., Butler, J., Patterson, N., Capelli, C., Pascali, V. L., Scarnicci, F., Ruiz-Linares, A., Groop, L., Saetta, A. A., Korkolopoulou, P., Seligsohn, U., Waliszewska, A., Schirmer, C., Ardlie, K., Ramos, A., Nemesh, J., Arbeitman, L., Goldstein, D. B., Reich, D., & Hirschhorn, J. N.
- Affiliations
- Broad Institute (US)
- University of Oxford (GB)
- Università Cattolica del Sacro Cuore (IT)
- Lund University (SE)
- National and Kapodistrian University of Athens (GR)
- Sheba Medical Center (IL)
- Duke University (US)
- Corresponding author
- Price, Alkes L
- Reich, David
- Hirschhorn, Joel N
- ORCID
- Venue
- PLoS Genetics
- Publisher
- Public Library of Science (PLoS)
- Published
- 2008-01-18
- Volume
- 4
- Issue
- 1
- Pages
- e236
- ISSN
- 1553-7390 (ISSN-L)
- 1553-7404
- PMC
- PMC2211542
- OpenAlex
- W2117980841
- Cited by
- 327
- References
- 35
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 9 · 2023: 6 · 2022: 7 · 2021: 5 · 2020: 13 · 2019: 7 · 2018: 10 · 2017: 12 · 2016: 15 · 2015: 17 · 2014: 13 · 2013: 20 · 2012: 33
- FWCI
- 29.06
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS Genetics (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Oxford University Research Archive (ORA) (University of Oxford) (acceptedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- UCL Discovery (University College London) (submittedVersion)
- Figshare (submittedVersion, cc-by)
- Lund University Publications (Lund University) (submittedVersion)
- Funders
- American Diabetes Association
- March of Dimes Foundation
- Richard and Susan Smith Family Foundation
- Massachusetts General Hospital
- University of Pennsylvania
- Emory University
- Northwestern University
- University of Pittsburgh
- Louisiana State University
- Broad Institute
- National Institutes of Health (6u54rr020278-06)
- School of Medicine, Emory University
- National Institute of Mental Health (MH59566, MH-60870, MH-059565, MH067257, MH-061675, MH-59586, R01MH059566, R01MH059571, MH-059571, R01MH060879, R01MH059565, R01MH060870, R01MH063420, U01 MH-060879, R01MH061675, R01MH059586, R01MH059588, MH63420, R01MH067257, MH-59587, MH-059588, R01MH059587)
- National Human Genome Research Institute (U01HG004168)
- National Institute of Neurological Disorders and Stroke
- National Center for Research Resources (U54-RR020278)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Forensic and Genetic Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Social Sciences › Anthropology › Race, Genetics, and Society
- Keywords
- European Americans, population structure, ancestry inference, population stratification, genetic association studies, Ashkenazi Jewish ancestry, ancestry informative markers, false positive association
- MeSH terms
- Bipolar Disorder, DNA, Genetic Markers, Genetics, Population, Geography, Humans, Jews, Multiple Sclerosis, Parkinson Disease, United States, Genetic Variation, Reproducibility of Results, Inflammatory Bowel Diseases, Genome, Human, Case-Control Studies, Oligonucleotide Array Sequence Analysis, White People
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