Analysis and application of European genetic substructure using 300 K SNP information
Open accessAbstract
European population genetic substructure was examined in a diverse set of >1,000 individuals of European descent, each genotyped with >300 K SNPs. Both STRUCTURE and principal component analyses (PCA) showed the largest division/principal component (PC) differentiated northern from southern European ancestry. A second PC further separated Italian, Spanish, and Greek individuals from those of Ashkenazi Jewish ancestry as well as distinguishing among northern European populations. In separate analyses of northern European participants other substructure relationships were discerned showing a west to east gradient. Application of this substructure information was critical in examining a real dataset in whole genome association (WGA) analyses for rheumatoid arthritis in European Americans to reduce false positive signals. In addition, two sets of European substructure ancestry informative markers (ESAIMs) were identified that provide substantial substructure information. The results provide further insight into European population genetic substructure and show that this information can be used for improving error rates in association testing of candidate genes and in replication studies of WGA scans.
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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.
“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 [48]
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- Authors
- Tian, C., Plenge, R. M., Ransom, M., Lee, A., Villoslada, P., Selmi, C., Klareskog, L., Pulver, A. E., Qi, L., Gregersen, P. K., & Seldin, M. F.
- Affiliations
- University of California, Davis (US)
- Broad Institute (US)
- Northwell Health (US)
- Centro de Investigación Médica Aplicada (ES)
- University of Milan (IT)
- Karolinska University Hospital (SE)
- Johns Hopkins University (US)
- Corresponding author
- Seldin, Michael F
- ORCID
- Venue
- PLoS Genetics
- Publisher
- Public Library of Science (PLoS)
- Published
- 2008-01-18
- Volume
- 4
- Issue
- 1
- Pages
- e4
- ISSN
- 1553-7390 (ISSN-L)
- 1553-7404
- PMC
- PMC2211544
- OpenAlex
- W2095119242
- Cited by
- 247
- References
- 44
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 3 · 2023: 4 · 2022: 3 · 2021: 3 · 2020: 8 · 2019: 8 · 2018: 5 · 2017: 6 · 2016: 11 · 2015: 10 · 2014: 8 · 2013: 18 · 2012: 25
- FWCI
- 24.76
- 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)
- Archivio Istituzionale della Ricerca (Universita Degli Studi Di Milano) (submittedVersion, cc-by)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion, cc-by)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK071185, DK071185)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR044422, AR050267, AR-44422, R01AR050267)
- 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
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic diversity and population structure
- Keywords
- population stratification, ancestry informative markers, European Americans, rheumatoid arthritis, whole-genome association studies, false positive signals, Ashkenazi Jewish ancestry, structure, principal component analysis, replication study
- MeSH terms
- Algorithms, Arthritis, Rheumatoid, Bayes Theorem, DNA, Genetic Markers, Genetics, Population, Geography, Humans, Ireland, Jews, Neoplasms, United States, Genetic Variation, Cluster Analysis, Case-Control Studies, Polymorphism, Single Nucleotide, Principal Component Analysis, White People
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