Detecting association in a case-control study while correcting for population stratification.
Case-control studies are subject to the problem of population stratification, which can occur in ethnically mixed populations and can lead to significant associations being detected at loci that have nothing to do with disease. Here, we describe a way to measure and correct for stratification by genotyping a moderate number of unlinked genetic markers in the same set of cases and controls in which a candidate association was found. The average of association statistics across the markers directly measures stratification. By dividing the candidate association statistic by this average, a P-value can be obtained that corrects for stratification.
Reich
D E
DE
Whitehead Institute/MIT Center for Genome Research, Cambridge, Massachusetts 02142, USA. reich@genome.wi.mit.edu
Goldstein
D B
DB
D016022:Case-Control Studies; D002874:Chromosome Mapping / Q000706:statistics & numerical data*; D005006:Ethnicity / Q000706:statistics & numerical data*; D005787:Gene Frequency; D006801:Humans; D015810:Linkage Disequilibrium; D008957:Models, Genetic; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D015983:Selection Bias