title: Matching on Race and Ethnicity in Case-Control Studies as a Means of Control for Population Stratification.
abstract: Some investigators argue that controlling for self-reported race or ethnicity, either in statistical analysis or in study design, is sufficient to mitigate unwanted influence from population stratification. In this report, we evaluated the effectiveness of a study design involving matching on self-reported ethnicity and race in minimizing bias due to population stratification within an ethnically admixed population in California. We estimated individual genetic ancestry using structured association methods and a panel of ancestry informative markers, and observed no statistically significant difference in distribution of genetic ancestry between cases and controls (P=0.46). Stratification by Hispanic ethnicity showed similar results. We evaluated potential confounding by genetic ancestry after adjustment for race and ethnicity for 1260 candidate gene SNPs, and found no major impact (>10%) on risk estimates. In conclusion, we found no evidence of confounding of genetic risk estimates by population substructure using this matched design. Our study provides strong evidence supporting the race- and ethnicity-matched case-control study design as an effective approach to minimizing systematic bias due to differences in genetic ancestry between cases and controls.
authors.affiliation: School of Public Health, University of California Berkeley, Berkeley.
authors.forename: Anand P
authors.initials: AP
authors.lastname: Chokkalingam
authors.affiliation: Vanderbilt University Medical Center, Vanderbilt University, Nashville, Tennessee.
authors.forename: Melinda C
authors.initials: MC
authors.lastname: Aldrich
authors.affiliation: School of Public Health, University of California Berkeley, Berkeley.
authors.forename: Karen
authors.initials: K
authors.lastname: Bartley
authors.affiliation: School of Public Health, University of California Berkeley, Berkeley.
authors.forename: Ling-I
authors.initials: LI
authors.lastname: Hsu
authors.affiliation: School of Public Health, University of California Berkeley, Berkeley.
authors.forename: Catherine
authors.initials: C
authors.lastname: Metayer
authors.affiliation: School of Public Health, University of California Berkeley, Berkeley.
authors.forename: Lisa F
authors.initials: LF
authors.lastname: Barcellos
authors.affiliation: Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, California.
authors.forename: Joseph L
authors.initials: JL
authors.lastname: Wiemels
authors.affiliation: Department of Neurological Surgery, University of California, San Francisco San Francisco, California.
authors.forename: John K
authors.initials: JK
authors.lastname: Wiencke
authors.affiliation: School of Public Health, University of California Berkeley, Berkeley.
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Buffler
authors.affiliation: School of Public Health, University of California Berkeley, Berkeley.
authors.forename: Steve
authors.initials: S
authors.lastname: Selvin
keywords: Case-control; Genetic susceptibility; Matching; Population stratification