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Demonstrating stratification in a European American population

Demonstrating stratification in a European American population 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 controversial 1,2,3,4 . Empirical studies have found little evidence of stratification in European-derived populations, but potentially significant levels of stratification could not be ruled out 5,6,7 . We studied a European American panel discordant for height, a heritable trait that varies widely across Europe 8 . Genotyping 178 SNPs and applying standard analytical methods 6,9,10,11 yielded no evidence of stratification. But a SNP in the gene LCT that varies widely in frequency across Europe 12 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. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Nature Genetics Springer Journals

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References (32)

Publisher
Springer Journals
Copyright
Copyright © 2005 by Nature Publishing Group
Subject
Biomedicine; Biomedicine, general; Human Genetics; Cancer Research; Agriculture; Gene Function; Animal Genetics and Genomics
ISSN
1061-4036
eISSN
1546-1718
DOI
10.1038/ng1607
Publisher site
See Article on Publisher Site

Abstract

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 controversial 1,2,3,4 . Empirical studies have found little evidence of stratification in European-derived populations, but potentially significant levels of stratification could not be ruled out 5,6,7 . We studied a European American panel discordant for height, a heritable trait that varies widely across Europe 8 . Genotyping 178 SNPs and applying standard analytical methods 6,9,10,11 yielded no evidence of stratification. But a SNP in the gene LCT that varies widely in frequency across Europe 12 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.

Journal

Nature GeneticsSpringer Journals

Published: Jul 24, 2005

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