Genes mirror geography within Europe
Open accessAbstract
Understanding the genetic structure of human populations is of fundamental interest to medical, forensic and anthropological sciences. Advances in high-throughput genotyping technology have markedly improved our understanding of global patterns of human genetic variation and suggest the potential to use large samples to uncover variation among closely spaced populations. Here we characterize genetic variation in a sample of 3,000 European individuals genotyped at over half a million variable DNA sites in the human genome. Despite low average levels of genetic differentiation among Europeans, we find a close correspondence between genetic and geographic distances; indeed, a geographical map of Europe arises naturally as an efficient two-dimensional summary of genetic variation in Europeans. The results emphasize that when mapping the genetic basis of a disease phenotype, spurious associations can arise if genetic structure is not properly accounted for. In addition, the results are relevant to the prospects of genetic ancestry testing; an individual's DNA can be used to infer their geographic origin with surprising accuracy-often to within a few hundred kilometres.
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European Americans have a history of admixture of many genetically distinct European populations.
“European Americans, however, have a history of admixture of many genetically distinct European populations.27,28”
From The genetic ancestry of African Americans, Latinos, and European Americans across the United States (2015) · cites this paper as [27]
The paper reports genetic structure among European populations (Abstract; page unavailable) and notes some individuals with mixed grandparental ancestry. It does not establish a history of admixture among European Americans; the Methods say individuals with putative origins outside Europe, including Europeans from the USA, were excluded. (LLM, conf=0.82)
Experimental — accuracy not yet measuredRegions 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).
“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”
From The genetic ancestry of African Americans, Latinos, and European Americans across the United States (2015) · cites this paper as [27]
The Methods section (Principal components analysis; page unavailable) says the authors filtered regions of strong linkage disequilibrium to avoid PCA artefacts and removed inversion regions, supporting the claim about detecting population substructure with PCA. Our copy does not say that these regions confound admixture mapping; it discusses genome-wide association studies instead. (LLM, conf=0.87)
Experimental — accuracy not yet measuredThe use of four-grandparent birth-country has been utilized as a proxy for assessing ancestry.
“The use of four-grandparent birth-country has been utilized as a proxy for assessing ancestry.27,63”
From The genetic ancestry of African Americans, Latinos, and European Americans across the United States (2015) · cites this paper as [27]
The block bootstrap gives better variance estimates than the jackknife for these pairwise allele frequency comparisons.
“This gives better variance estimates than the jackknife for these pairwise allele frequency comparisons34.”
From Paths and timings of the peopling of Polynesia inferred from genomic networks (2021) · cites this paper as [34]
The Methods Summary describes leave-one-out cross-validation, and the Methods describe SNP filtering and association simulations. Neither those passages nor searches for “block bootstrap,” “jackknife,” and “variance estimates” address a comparison of the two methods for pairwise allele-frequency comparisons. (LLM, conf=0.75)
Experimental — accuracy not yet measuredThe alignment of the first two genetic PCs with geography and the clustering of individuals by European country are consistent with the results of a previous larger study of European genetic structure.
“The alignment of the first two genetic PCs with geography and the clustering of individuals by European country are consistent with the results of a previous larger study of European genetic structure [28].”
From Genome-Wide Association Studies of Quantitatively Measured Skin, Hair, and Eye Pigmentation in Four European Populations (2012) · cites this paper as [28]
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Population phenomena inflate genetic associations of complex social traits
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The Spread of Buddhist Culture to China between the Third and Seventh Centuries
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- Authors
- Novembre, J., Johnson, T., Bryc, K., Kutalik, Z., Boyko, A. R., Auton, A., Indap, A., King, K. S., Bergmann, S., Nelson, M. R., Stephens, M., & Bustamante, C. D.
- Affiliations
- University of California, Los Angeles (US)
- SIB Swiss Institute of Bioinformatics (CH)
- Cornell University (US)
- GlaxoSmithKline (United States) (US)
- University of Chicago (US)
- Corresponding author
- Novembre, John
- ORCID
- Venue
- Nature
- Published
- 2008-08-31
- Volume
- 456
- Issue
- 7218
- Pages
- 98-101
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC2735096
- OpenAlex
- W2133148918
- Cited by
- 1,479
- References
- 31
- Citations by year
- 2026: 39 · 2025: 52 · 2024: 59 · 2023: 82 · 2022: 79 · 2021: 88 · 2020: 92 · 2019: 77 · 2018: 102 · 2017: 78 · 2016: 89 · 2015: 92 · 2014: 92 · 2013: 86 · 2012: 99
- FWCI
- 51.67
- Type
- journal article
- Language
- en
- Update notices
- erratum (2008-11-13)
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- IRIS (submittedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- SERVAL (Université de Lausanne) (submittedVersion, other-oa)
- Funders
- National Science Foundation
- GlaxoSmithKline
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
- National Institutes of Health
- National Institute of General Medical Sciences (R01GM083606)
- Topics
- 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
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- human genetic variation, genetic ancestry, genetic distance, geographic distance, population structure, genome-wide association study, genetic ancestry testing
- MeSH terms
- Emigration and Immigration, Europe, Genetics, Population, Genotype, Geography, Humans, Phylogeny, Genetic Variation, Genome, Human, Sample Size, Quantitative Trait, Heritable, Polymorphism, Single Nucleotide, Principal Component Analysis, Genome-Wide Association Study
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