title: Demonstrating stratification in a European American population.
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. Empirical studies have found little evidence of stratification in European-derived populations, but potentially significant levels of stratification could not be ruled out. We studied a European American panel discordant for height, a heritable trait that varies widely across Europe. Genotyping 178 SNPs and applying standard analytical methods yielded no evidence of stratification. But a SNP in the gene LCT that varies widely in frequency across Europe 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.
authors.affiliation: Program in Genomics and Division of Endocrinology, Children's Hospital, 300 Longwood Avenue, Boston, Massachusetts 02115, USA.
authors.forename: Catarina D
authors.initials: CD
authors.lastname: Campbell
authors.forename: Elizabeth L
authors.initials: EL
authors.lastname: Ogburn
authors.forename: Kathryn L
authors.initials: KL
authors.lastname: Lunetta
authors.forename: Helen N
authors.initials: HN
authors.lastname: Lyon
authors.forename: Matthew L
authors.initials: ML
authors.lastname: Freedman
authors.forename: Leif C
authors.initials: LC
authors.lastname: Groop
authors.forename: David
authors.initials: D
authors.lastname: Altshuler
authors.forename: Kristin G
authors.initials: KG
authors.lastname: Ardlie
authors.forename: Joel N
authors.initials: JN
authors.lastname: Hirschhorn
mesh_terms: D005828:Genetics, Population; D005838:Genotype; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D044465:White People / Q000235:genetics*