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Genes mirror geography within Europe

An Addendum to this article was published on 13 November 2008

Abstract

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 populations1,2,3,4,5. 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 testing6; 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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Figure 1: Population structure within Europe.
Figure 2: Performance of assignment method.

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References

  1. Jakobsson, M. et al. Genotype, haplotype and copy-number variation in worldwide human populations. Nature 451, 998–1003 (2008)

    Article  ADS  CAS  Google Scholar 

  2. Li, J. Z. et al. Worldwide human relationships inferred from genome-wide patterns of variation. Science 319, 1100–1104 (2008)

    Article  ADS  CAS  Google Scholar 

  3. Wellcome Trust Case Control Consortium. Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature 447, 661–678 (2007)

  4. Tian, C. et al. Analysis and application of European genetic substructure using 300K SNP information. PLoS Genet. 4, e4 (2008)

    Article  Google Scholar 

  5. Price, A. L. et al. Discerning the ancestry of European Americans in genetic association studies. PLoS Genet. 4, e236 (2008)

    Article  Google Scholar 

  6. Shriver, M. D. & Kittles, R. A. Genetic ancestry and the search for personalized genetic histories. Nature Rev. Genet. 5, 611–618 (2004)

    Article  CAS  Google Scholar 

  7. Nelson, M. R. et al. The Population Reference Sample (POPRES): a resource for population, disease, and pharmacological genetics research. Am. J. Hum. Genet. (in the press)

  8. Patterson, N., Price, A. & Reich, D. Population structure and eigenanalysis. PLoS Genet. 2, e190 (2006)

    Article  Google Scholar 

  9. Novembre, J. & Stephens, M. Interpreting principal component analyses of spatial population genetic variation. Nature Genet. 40, 646–649 (2008)

    Article  CAS  Google Scholar 

  10. Menozzi, P., Piazza, A. & Cavalli-Sforza, L. Synthetic maps of human gene frequencies in Europeans. Science 201, 786–792 (1978)

    Article  ADS  CAS  Google Scholar 

  11. Campbell, C. D. et al. Demonstrating stratification in a European American population. Nature Genet. 37, 868–872 (2005)

    Article  CAS  Google Scholar 

  12. Price, A. L. et al. Principal components analysis corrects for stratification in genome-wide association studies. Nature Genet. 38, 904–909 (2006)

    Article  CAS  Google Scholar 

  13. McCarthy, M. I. et al. Genome-wide association studies for complex traits: consensus, uncertainty and challenges. Nature Rev. Genet. 9, 356–369 (2008)

    Article  CAS  Google Scholar 

  14. Zhu, X., Zhang, S., Zhao, H. & Cooper, R. S. Association mapping, using a mixture model for complex traits. Genet. Epidemiol. 23, 181–196 (2002)

    Article  Google Scholar 

  15. Weedon, M. N. et al. Genome-wide association analysis identifies 20 loci that influence adult height. Nature Genet. 40, 575–583 (2008)

    Article  CAS  Google Scholar 

  16. Lettre, G. et al. Identification of ten loci associated with height highlights new biological pathways in human growth. Nature Genet. 40, 584–591 (2008)

    Article  CAS  Google Scholar 

  17. Cavalli-Sforza, L. L., Menozzi, P. & Piazza, A. The History and Geography of Human Genes 292 (Princeton Univ. Press, 1994)

    MATH  Google Scholar 

  18. Bauchet, M. et al. Measuring European population stratification with microarray genotype data. Am. J. Hum. Genet. 80, 948–956 (2007)

    Article  CAS  Google Scholar 

  19. Weir, B. S. & Cockerham, C. C. Estimating F-statistics for the analysis of population structure. Evolution 38, 1358–1370 (1984)

    CAS  Google Scholar 

  20. Eberle, M. A. & Kruglyak, L. An analysis of strategies for discovery of single nucleotide polymorphisms. Genet. Epidemiol. 19, S29–S35 (2000)

    Article  Google Scholar 

  21. Clark, A. G., Hubisz, M. J., Bustamante, C. D., Williamson, S. H. & Nielsen, R. Ascertainment bias in studies of human genome-wide polymorphism. Genome Res. 15, 1496–1502 (2005)

    Article  CAS  Google Scholar 

  22. Slatkin, M. Rare alleles as indicators of gene flow. Evolution 39, 53–65 (1985)

    Article  Google Scholar 

  23. Falush, D., Stephens, M. & Pritchard, J. K. Inference of population structure using multilocus genotype data: linked loci and correlated allele frequencies. Genetics 164, 1567–1587 (2003)

    CAS  PubMed  PubMed Central  Google Scholar 

  24. Tang, H., Coram, M., Wang, P., Zhu, X. & Risch, N. Reconstructing genetic ancestry blocks in admixed individuals. Am. J. Hum. Genet. 79, 1–12 (2006)

    Article  CAS  Google Scholar 

  25. Hellenthal, G., Auton, A. & Falush, D. Inferring human colonization history using a copying model. PLoS Genet. 4, e1000078 (2008)

    Article  Google Scholar 

  26. Kooner, J. et al. Genome-wide scan identifies variation in MLXIPL associated with plasma triglycerides. Nature Genet. 40, 149–151 (2008)

    Article  CAS  Google Scholar 

  27. Firmann, M. et al. The CoLaus study: A population-based study to investigate the epidemiology and genetic determinants of cardiovascular risk factors and metabolic syndrome. BMC Cardiovasc. Dis. 8, 6 (2008)

    Article  Google Scholar 

  28. Purcell, S. et al. PLINK: A tool set for whole-genome association and population-based linkage analyses. Am. J. Hum. Genet. 81, 559–575 (2007)

    Article  CAS  Google Scholar 

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Acknowledgements

We thank J. Kooner and J. Chambers of the LOLIPOP study and G. Waeber, P. Vollenweider, D. Waterworth, J. S. Beckmann, M. Bochud and V. Mooser of the CoLaus study for providing access to their collections. Financial support was provided by the Giorgi-Cavaglieri Foundation (S.B.), the Swiss National Science Foundation (S.B.), US National Science Foundation Postdoctoral Fellowship in Bioinformatics (J.N.), US National Institutes of Health (M.S., C.D.B.) and GlaxoSmithKline (M.R.N.).

Author Contributions M.R.N. coordinated sample collection and genotyping. K.S.K., A.I., J.N. and A.R.B. performed quality control and prepared genotypic and demographic data for further analyses. C.B., M.S., M.R.N., S.B., J.N., T.J., K.B., Z.K., A.R.B. and A.A. all contributed to the design of analyses. J.N., S.B., T.J., K.B. and Z.K. performed PCA analyses. M.S. and J.N. designed and performed assignment-based analyses. T.J. and J.N. performed genome-wide association simulations. J.N., C.B., M.S., M.R.N. and A.A. wrote the paper. All authors discussed the results and commented on the manuscript.

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Correspondence to John Novembre.

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Novembre, J., Johnson, T., Bryc, K. et al. Genes mirror geography within Europe. Nature 456, 98–101 (2008). https://doi.org/10.1038/nature07331

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