Nature Genetics
37, 868 - 872 (2005)
Published online: 24 July 2005; | doi:10.1038/ng1607
Demonstrating stratification in a European American populationCatarina D Campbell1, 2, Elizabeth L Ogburn1, Kathryn L Lunetta3, 8, Helen N Lyon1, 2, Matthew L Freedman4, 5, 6, Leif C Groop7, David Altshuler2, 4, 5, Kristin G Ardlie3
& Joel N Hirschhorn1, 2, 41
Program in Genomics and Division of Endocrinology, Children's Hospital, 300 Longwood Avenue, Boston, Massachusetts 02115, USA. 2
Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA. 3
Genomics Collaborative Inc., 99 Erie St., Cambridge, Massachusetts 02139, USA. 4
Broad Institute of Harvard and MIT, One Kendall Square, Cambridge, Massachusetts 02139, USA. 5
Departments of Medicine and Molecular Biology, Massachusetts General Hospital, 55 Fruit Street, Boston, Massachusetts 02114, USA. 6
Department of Hematology-Oncology, Massachusetts General Hospital, Boston, Massachusetts 02114, USA. 7
Department of Clinical Science/Diabetes and Endocrinology, University Hospital, Lund University, Malmö, Sweden. 8
Present address: Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts 02118, USA.
Correspondence should be addressed to Joel N Hirschhorn joelh@broad.mit.edu Population stratification occurs in case-control association studies when allele frequencies differ between cases and controls because of ancestry. Stratification may lead to false positive associations, although this issue remains controversial1,
2,
3,
4. Empirical studies have found little evidence of stratification in European-derived populations, but potentially significant levels of stratification could not be ruled out5,
6,
7. We studied a European American panel discordant for height, a heritable trait that varies widely across Europe8. Genotyping 178 SNPs and applying standard analytical methods6,
9,
10,
11 yielded no evidence of stratification. But a SNP in the gene LCT that varies widely in frequency across Europe12 was strongly associated with height (P < 10-6). This apparent association was largely or completely due to stratification; rematching individuals on the basis of European ancestry greatly reduced the apparent association, and no association was observed in Polish or Scandinavian individuals. The failure of standard methods to detect this stratification indicates that new methods may be required.
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