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. Findings. 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.
| Original language | English (US) |
|---|---|
| Article number | 260 |
| Journal | BMC Research Notes |
| Volume | 2 |
| DOIs | |
| State | Published - 2009 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
- Medicine(all)
Cite this
Evaluation of self-reported ethnicity in a case-control population : The stroke prevention in young women study. / Mez, Jesse B.; Cole, John W.; Howard, Timothy D.; MacClellan, Leah R.; Stine, Oscar C.; O'Connell, Jeffery R.; Wozniak, Marcella A.; Stern, Barney; Sorkin, John D.; Mitchell, Braxton D.; Kittner, Steven J.
In: BMC Research Notes, Vol. 2, 260, 2009.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Evaluation of self-reported ethnicity in a case-control population
T2 - The stroke prevention in young women study
AU - Mez, Jesse B.
AU - Cole, John W.
AU - Howard, Timothy D.
AU - MacClellan, Leah R.
AU - Stine, Oscar C.
AU - O'Connell, Jeffery R.
AU - Wozniak, Marcella A.
AU - Stern, Barney
AU - Sorkin, John D.
AU - Mitchell, Braxton D.
AU - Kittner, Steven J.
PY - 2009
Y1 - 2009
N2 - 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. Findings. 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.
AB - 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. Findings. 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.
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U2 - 10.1186/1756-0500-2-260
DO - 10.1186/1756-0500-2-260
M3 - Article
VL - 2
JO - BMC Research Notes
JF - BMC Research Notes
SN - 1756-0500
M1 - 260
ER -