title: Examining population stratification via individual ancestry estimates versus self-reported race.
abstract: Population stratification has the potential to affect the results of genetic marker studies. Estimating individual ancestry provides a continuous measure to assess population structure in case-control studies of complex disease, instead of using self-reported racial groups. We estimate individual ancestry using the Federal Bureau of Investigation CODIS Core short tandem repeat set of 13 loci using two different analysis methods in a case-control study of early-onset lung cancer. Individual ancestry proportions were estimated for "European" and "West African" groups using published allele frequencies. The majority of Caucasian, non-Hispanics had >50% European ancestry, whereas the majority of African Americans had <20% European ancestry, regardless of ancestry estimation method, although significant overlap by self-reported race and ancestry also existed. When we further investigated the effect of ancestry and self-reported race on the frequency of a lung cancer risk genotype, we found that the frequency of the GSTM1 null genotype varies by individual European ancestry and case-control status within self-reported race (particularly for African Americans). Genetic risk models showed that adjusting for individual European ancestry provided a better fit to the data compared with the model with no group adjustment or adjustment for self-reported race. This study suggests that significant population substructure differences exist that self-reported race alone does not capture and that individual ancestry may be confounded with disease status and/or a candidate gene risk genotype.
authors.affiliation: Cancer Prevention and Control Program, H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, Florida 33612, USA. barnhojs@moffitt.usf.edu
authors.forename: Jill S
authors.initials: JS
authors.lastname: Barnholtz-Sloan
authors.forename: Ranajit
authors.initials: R
authors.lastname: Chakraborty
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Sellers
authors.forename: Ann G
authors.initials: AG
authors.lastname: Schwartz
mesh_terms: D044383:Black People / Q000235:genetics*; D016022:Case-Control Studies; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D008962:Models, Theoretical; D010375:Pedigree; D015203:Reproducibility of Results; D018570:Risk Assessment; D020080:Tandem Repeat Sequences; D044465:White People / Q000235:genetics*; D001741:Black or African American
chemical_list: D005982:Glutathione Transferase