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The Population Reference Sample, POPRES: A Resource for Population, Disease, and Pharmacological Genetics Research
Open accessAbstract
Technological and scientific advances, stemming in large part from the Human Genome and HapMap projects, have made large-scale, genome-wide investigations feasible and cost effective. These advances have the potential to dramatically impact drug discovery and development by identifying genetic factors that contribute to variation in disease risk as well as drug pharmacokinetics, treatment efficacy, and adverse drug reactions. In spite of the technological advancements, successful application in biomedical research would be limited without access to suitable sample collections. To facilitate exploratory genetics research, we have assembled a DNA resource from a large number of subjects participating in multiple studies throughout the world. This growing resource was initially genotyped with a commercially available genome-wide 500,000 single-nucleotide polymorphism panel. This project includes nearly 6,000 subjects of African-American, East Asian, South Asian, Mexican, and European origin. Seven informative axes of variation identified via principal-component analysis (PCA) of these data confirm the overall integrity of the data and highlight important features of the genetic structure of diverse populations. The potential value of such extensively genotyped collections is illustrated by selection of genetically matched population controls in a genome-wide analysis of abacavir-associated hypersensitivity reaction. We find that matching based on country of origin, identity-by-state distance, and multidimensional PCA do similarly well to control the type I error rate. The genotype and demographic data from this reference sample are freely available through the NCBI database of Genotypes and Phenotypes (dbGaP).
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“Regions of the genome that have structural variation or show strong linkage disequilibrium (LD) have been shown both to confound admixture mapping and to influence the detection of population substructure in studies using Principal Components Analysis (PCA).27,63,65”
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“The use of four-grandparent birth-country has been utilized as a proxy for assessing ancestry.27,63”
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Additional file 2 of Genetic history of East-Central Europe in the first millennium CE
Stolarek, I., Zeńczak, M., Handschuh, L., Juras, A., Marcinkowska, M., Spinek, A. E., Dębski, A., Matla, M., Kóčka-Krenz, H., Piontek, J., et al. (2023) · Figshare · doi:10.6084/m9.figshare.23740746
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Additional file 6 of Genetic history of East-Central Europe in the first millennium CE
Stolarek, I., Zeńczak, M., Handschuh, L., Juras, A., Marcinkowska, M., Spinek, A. E., Dębski, A., Matla, M., Kóčka-Krenz, H., Piontek, J., et al. (2023) · Figshare · doi:10.6084/m9.figshare.23740758
Additional file 10 of Genetic history of East-Central Europe in the first millennium CE
Stolarek, I., Zeńczak, M., Handschuh, L., Juras, A., Marcinkowska, M., Spinek, A. E., Dębski, A., Matla, M., Kóčka-Krenz, H., Piontek, J., et al. (2023) · Figshare · doi:10.6084/m9.figshare.23740770
Additional file 5 of Genetic history of East-Central Europe in the first millennium CE
Stolarek, I., Zeńczak, M., Handschuh, L., Juras, A., Marcinkowska, M., Spinek, A. E., Dębski, A., Matla, M., Kóčka-Krenz, H., Piontek, J., et al. (2023) · Figshare · doi:10.6084/m9.figshare.23740755
Additional file 11 of Genetic history of East-Central Europe in the first millennium CE
Stolarek, I., Zeńczak, M., Handschuh, L., Juras, A., Marcinkowska, M., Spinek, A. E., Dębski, A., Matla, M., Kóčka-Krenz, H., Piontek, J., et al. (2023) · Figshare · doi:10.6084/m9.figshare.23740773
Additional file 4 of Genetic history of East-Central Europe in the first millennium CE
Stolarek, I., Zeńczak, M., Handschuh, L., Juras, A., Marcinkowska, M., Spinek, A. E., Dębski, A., Matla, M., Kóčka-Krenz, H., Piontek, J., et al. (2023) · Figshare · doi:10.6084/m9.figshare.23740752
Additional file 8 of Genetic history of East-Central Europe in the first millennium CE
Stolarek, I., Zeńczak, M., Handschuh, L., Juras, A., Marcinkowska, M., Spinek, A. E., Dębski, A., Matla, M., Kóčka-Krenz, H., Piontek, J., et al. (2023) · Figshare · doi:10.6084/m9.figshare.23740764
Additional file 1 of Genetic history of East-Central Europe in the first millennium CE
Stolarek, I., Zeńczak, M., Handschuh, L., Juras, A., Marcinkowska, M., Spinek, A. E., Dębski, A., Matla, M., Kóčka-Krenz, H., Piontek, J., et al. (2023) · Figshare · doi:10.6084/m9.figshare.23740743
Additional file 3 of Genetic history of East-Central Europe in the first millennium CE
Stolarek, I., Zeńczak, M., Handschuh, L., Juras, A., Marcinkowska, M., Spinek, A. E., Dębski, A., Matla, M., Kóčka-Krenz, H., Piontek, J., et al. (2023) · Figshare · doi:10.6084/m9.figshare.23740749
Additional file 7 of Genetic history of East-Central Europe in the first millennium CE
Stolarek, I., Zeńczak, M., Handschuh, L., Juras, A., Marcinkowska, M., Spinek, A. E., Dębski, A., Matla, M., Kóčka-Krenz, H., Piontek, J., et al. (2023) · Figshare · doi:10.6084/m9.figshare.23740761
Additional file 9 of Genetic history of East-Central Europe in the first millennium CE
Stolarek, I., Zeńczak, M., Handschuh, L., Juras, A., Marcinkowska, M., Spinek, A. E., Dębski, A., Matla, M., Kóčka-Krenz, H., Piontek, J., et al. (2023) · Figshare · doi:10.6084/m9.figshare.23740767
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Metadata
- Authors
- Nelson, M. R., Bryc, K., King, K. S., Indap, A., Boyko, A. R., Novembre, J., Briley, L. P., Maruyama, Y., Waterworth, D. M., Waeber, G., Vollenweider, P., Oksenberg, J. R., Hauser, S. L., Stirnadel, H. A., Kooner, J. S., Chambers, J. C., Jones, B., Mooser, V., Bustamante, C. D., Roses, A. D., Burns, D. K., Ehm, M. G., & Lai, E. H.
- Affiliations
- GlaxoSmithKline (United States) (US)
- Cornell University (US)
- University of California, Los Angeles (US)
- Centre Hospitalier Universitaire Vaudois (CH)
- University of California, San Francisco (US)
- Imperial College London (GB)
- Corresponding author
- Nelson, Matthew R.
- ORCID
- Venue
- The American Journal of Human Genetics
- Publisher
- Elsevier BV
- Published
- 2008-09
- Volume
- 83
- Issue
- 3
- Pages
- 347-358
- ISSN
- 0002-9297 (ISSN-L)
- PMC
- PMC2556436
- OpenAlex
- W1981638214
- Cited by
- 293
- References
- 36
- Citations by year
- 2026: 3 · 2025: 8 · 2024: 6 · 2023: 17 · 2022: 7 · 2021: 2 · 2020: 10 · 2019: 13 · 2018: 47 · 2017: 13 · 2016: 17 · 2015: 25 · 2014: 21 · 2013: 22 · 2012: 27
- FWCI
- 10.47
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- The American Journal of Human Genetics (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- IRIS (submittedVersion)
- SERVAL (Université de Lausanne) (submittedVersion)
- Funders
- GlaxoSmithKline
- Tri-Service General Hospital
- National Institutes of Health
- University of California, San Francisco
- National Institute of General Medical Sciences (R01GM083606)
- National Institute of Neurological Disorders and Stroke (R01NS046297)
- 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
- Social Sciences › Anthropology › Race, Genetics, and Society
- Keywords
- single nucleotide polymorphisms, genetic ancestry, population structure, genetic matching, abacavir hypersensitivity, pharmacogenetics, disease genetics, dbGaP
- MeSH terms
- Abacavir, Drug Hypersensitivity, Female, Genetics, Population, Genotype, Humans, Male, Pharmacogenetics, Dideoxynucleosides, Genome, Human, Case-Control Studies, Polymorphism, Single Nucleotide, Databases, Genetic, Population Groups, White People
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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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