The potential for enhancing the power of genetic association studies in African Americans through the reuse of existing genotype data

Gary K. Chen, Robert C. Millikan, Esther M. John, Christine B. Ambrosone, Leslie Bernstein, Wei Zheng, Jennifer Hu, Stephen J. Chanock, Regina G. Ziegler, Elisa V. Bandera, Brian E. Henderson, Christopher A. Haiman, Daniel O. Stram

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

We consider the feasibility of reusing existing control data obtained in genetic association studies in order to reduce costs for new studies. We discuss controlling for the population differences between cases and controls that are implicit in studies utilizing external control data. We give theoretical calculations of the statistical power of a test due to Bourgain et al (Am J Human Genet 2003), applied to the problem of dealing with case-control differences in genetic ancestry related to population isolation or population admixture. Theoretical results show that there may exist bounds for the non-centrality parameter for a test of association that places limits on study power even if sample sizes can grow arbitrarily large. We apply this method to data from a multi-center, geographically-diverse, genome-wide association study of breast cancer in African- American women. Our analysis of these data shows that admixture proportions differ by center with the average fraction of European admixture ranging from approximately 20% for participants from study sites in the Eastern United States to 25% for participants from West Coast sites. However, these differences in average admixture fraction between sites are largely counterbalanced by considerable diversity in individual admixture proportion within each study site. Our results suggest that statistical correction for admixture differences is feasible for future studies of African-Americans, utilizing the existing controls from the African-American Breast Cancer study, even if case ascertainment for the future studies is not balanced over the same centers or regions that supplied the controls for the current study.

Original languageEnglish
Article numbere1001096
JournalPLoS Genetics
Volume6
Issue number9
DOIs
StatePublished - Sep 1 2010

Fingerprint

African American
Genetic Association Studies
African Americans
genotype
Genotype
breast neoplasms
Breast Neoplasms
Population
Viverridae
cancer
Eastern United States
Genome-Wide Association Study
Sample Size
genet
data analysis
ancestry
testing
Costs and Cost Analysis
coasts
genome

ASJC Scopus subject areas

  • Genetics
  • Molecular Biology
  • Ecology, Evolution, Behavior and Systematics
  • Cancer Research
  • Genetics(clinical)

Cite this

Chen, G. K., Millikan, R. C., John, E. M., Ambrosone, C. B., Bernstein, L., Zheng, W., ... Stram, D. O. (2010). The potential for enhancing the power of genetic association studies in African Americans through the reuse of existing genotype data. PLoS Genetics, 6(9), [e1001096]. https://doi.org/10.1371/journal.pgen.1001096

The potential for enhancing the power of genetic association studies in African Americans through the reuse of existing genotype data. / Chen, Gary K.; Millikan, Robert C.; John, Esther M.; Ambrosone, Christine B.; Bernstein, Leslie; Zheng, Wei; Hu, Jennifer; Chanock, Stephen J.; Ziegler, Regina G.; Bandera, Elisa V.; Henderson, Brian E.; Haiman, Christopher A.; Stram, Daniel O.

In: PLoS Genetics, Vol. 6, No. 9, e1001096, 01.09.2010.

Research output: Contribution to journalArticle

Chen, GK, Millikan, RC, John, EM, Ambrosone, CB, Bernstein, L, Zheng, W, Hu, J, Chanock, SJ, Ziegler, RG, Bandera, EV, Henderson, BE, Haiman, CA & Stram, DO 2010, 'The potential for enhancing the power of genetic association studies in African Americans through the reuse of existing genotype data', PLoS Genetics, vol. 6, no. 9, e1001096. https://doi.org/10.1371/journal.pgen.1001096
Chen, Gary K. ; Millikan, Robert C. ; John, Esther M. ; Ambrosone, Christine B. ; Bernstein, Leslie ; Zheng, Wei ; Hu, Jennifer ; Chanock, Stephen J. ; Ziegler, Regina G. ; Bandera, Elisa V. ; Henderson, Brian E. ; Haiman, Christopher A. ; Stram, Daniel O. / The potential for enhancing the power of genetic association studies in African Americans through the reuse of existing genotype data. In: PLoS Genetics. 2010 ; Vol. 6, No. 9.
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