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. 1999 Jul;65(1):220–228. doi: 10.1086/302449

Use of unlinked genetic markers to detect population stratification in association studies.

J K Pritchard 1, N A Rosenberg 1
PMCID: PMC1378093  PMID: 10364535

Abstract

We examine the issue of population stratification in association-mapping studies. In case-control studies of association, population subdivision or recent admixture of populations can lead to spurious associations between a phenotype and unlinked candidate loci. Using a model of sampling from a structured population, we show that if population stratification exists, it can be detected by use of unlinked marker loci. We show that the case-control-study design, using unrelated control individuals, is a valid approach for association mapping, provided that marker loci unlinked to the candidate locus are included in the study, to test for stratification. We suggest guidelines as to the number of unlinked marker loci to use.

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Selected References

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  1. Boehnke M., Langefeld C. D. Genetic association mapping based on discordant sib pairs: the discordant-alleles test. Am J Hum Genet. 1998 Apr;62(4):950–961. doi: 10.1086/301787. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bowcock A. M., Kidd J. R., Mountain J. L., Hebert J. M., Carotenuto L., Kidd K. K., Cavalli-Sforza L. L. Drift, admixture, and selection in human evolution: a study with DNA polymorphisms. Proc Natl Acad Sci U S A. 1991 Feb 1;88(3):839–843. doi: 10.1073/pnas.88.3.839. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Falk C. T., Rubinstein P. Haplotype relative risks: an easy reliable way to construct a proper control sample for risk calculations. Ann Hum Genet. 1987 Jul;51(Pt 3):227–233. doi: 10.1111/j.1469-1809.1987.tb00875.x. [DOI] [PubMed] [Google Scholar]
  4. Goldstein D. B., Ruiz Linares A., Cavalli-Sforza L. L., Feldman M. W. Genetic absolute dating based on microsatellites and the origin of modern humans. Proc Natl Acad Sci U S A. 1995 Jul 18;92(15):6723–6727. doi: 10.1073/pnas.92.15.6723. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Jorde L. B., Bamshad M. J., Watkins W. S., Zenger R., Fraley A. E., Krakowiak P. A., Carpenter K. D., Soodyall H., Jenkins T., Rogers A. R. Origins and affinities of modern humans: a comparison of mitochondrial and nuclear genetic data. Am J Hum Genet. 1995 Sep;57(3):523–538. doi: 10.1002/ajmg.1320570340. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Jorde L. B., Rogers A. R., Bamshad M., Watkins W. S., Krakowiak P., Sung S., Kere J., Harpending H. C. Microsatellite diversity and the demographic history of modern humans. Proc Natl Acad Sci U S A. 1997 Apr 1;94(7):3100–3103. doi: 10.1073/pnas.94.7.3100. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Lander E. S., Schork N. J. Genetic dissection of complex traits. Science. 1994 Sep 30;265(5181):2037–2048. doi: 10.1126/science.8091226. [DOI] [PubMed] [Google Scholar]
  8. Lazzeroni L. C., Lange K. A conditional inference framework for extending the transmission/disequilibrium test. Hum Hered. 1998 Mar-Apr;48(2):67–81. doi: 10.1159/000022784. [DOI] [PubMed] [Google Scholar]
  9. McKeigue P. M. Mapping genes underlying ethnic differences in disease risk by linkage disequilibrium in recently admixed populations. Am J Hum Genet. 1997 Jan;60(1):188–196. [PMC free article] [PubMed] [Google Scholar]
  10. Risch N., Merikangas K. The future of genetic studies of complex human diseases. Science. 1996 Sep 13;273(5281):1516–1517. doi: 10.1126/science.273.5281.1516. [DOI] [PubMed] [Google Scholar]
  11. Shriver M. D., Smith M. W., Jin L., Marcini A., Akey J. M., Deka R., Ferrell R. E. Ethnic-affiliation estimation by use of population-specific DNA markers. Am J Hum Genet. 1997 Apr;60(4):957–964. [PMC free article] [PubMed] [Google Scholar]
  12. Slatkin M. Inbreeding coefficients and coalescence times. Genet Res. 1991 Oct;58(2):167–175. doi: 10.1017/s0016672300029827. [DOI] [PubMed] [Google Scholar]
  13. Spielman R. S., Ewens W. J. A sibship test for linkage in the presence of association: the sib transmission/disequilibrium test. Am J Hum Genet. 1998 Feb;62(2):450–458. doi: 10.1086/301714. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Spielman R. S., McGinnis R. E., Ewens W. J. Transmission test for linkage disequilibrium: the insulin gene region and insulin-dependent diabetes mellitus (IDDM). Am J Hum Genet. 1993 Mar;52(3):506–516. [PMC free article] [PubMed] [Google Scholar]
  15. Thomson G., Robinson W. P., Kuhner M. K., Joe S., Klitz W. HLA and insulin gene associations with IDDM. Genet Epidemiol. 1989;6(1):155–160. doi: 10.1002/gepi.1370060129. [DOI] [PubMed] [Google Scholar]
  16. Wang D. G., Fan J. B., Siao C. J., Berno A., Young P., Sapolsky R., Ghandour G., Perkins N., Winchester E., Spencer J. Large-scale identification, mapping, and genotyping of single-nucleotide polymorphisms in the human genome. Science. 1998 May 15;280(5366):1077–1082. doi: 10.1126/science.280.5366.1077. [DOI] [PubMed] [Google Scholar]

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