title: Evaluation of self-reported ethnicity in a case-control population: the stroke prevention in young women study.
abstract: BACKGROUND
  Population-based association studies are used to identify common susceptibility variants for complex genetic traits. These studies are susceptible to confounding from unknown population substructure. Here we apply a model-based clustering approach to our case-control study of stroke among young women to examine if self-reported ethnicity can serve as a proxy for genetic ancestry.
  
  
  RESULTS
  A population-based case-control study of stroke among women aged 15-49 identified 361 cases of first ischemic stroke and 401 age-comparable control subjects. Thirty single nucleotide polymorphisms (SNPs) throughout the genome unrelated to stroke risk and with established ancestry-based allele frequency differences were genotyped in all participants. The Structure program was used to iteratively evaluate for K = 1 to 5 potential genetic-based subpopulations. Evaluating the population as a whole, the Structure output plateaued at K = 2 clusters. 98% of self-reported Caucasians had an estimated probability >/=50% of belonging to Cluster 1, while 94% of self-reported African-Americans had an estimated probability >/=50% of belonging to Cluster 2. Stratifying the participants by self-reported ethnicity and repeating the analyses revealed the presence of two clusters among Caucasians, suggesting that potential substructure may exist.
  
  
  CONCLUSIONS
  Among our combined sample of African-American and Caucasian participants there is no large unknown subpopulation and self-reported ethnicity can serve as a proxy for genetic ancestry. Ethnicity-specific analyses indicate that population substructure may exist among the Caucasian participants indicating that further studies are warranted.
authors.affiliation: Department of Neurology, University of Maryland School of Medicine, Baltimore, MD, USA. jcole@som.umaryland.edu.
authors.forename: Jesse B
authors.initials: JB
authors.lastname: Mez
authors.forename: John W
authors.initials: JW
authors.lastname: Cole
authors.forename: Timothy D
authors.initials: TD
authors.lastname: Howard
authors.forename: Leah R
authors.initials: LR
authors.lastname: Macclellan
authors.forename: Oscar C
authors.initials: OC
authors.lastname: Stine
authors.forename: Jeffery R
authors.initials: JR
authors.lastname: O'Connell
authors.forename: Marcella A
authors.initials: MA
authors.lastname: Wozniak
authors.forename: Barney J
authors.initials: BJ
authors.lastname: Stern
authors.forename: John D
authors.initials: JD
authors.lastname: Sorkin
authors.forename: Braxton D
authors.initials: BD
authors.lastname: Mitchell
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Kittner