Genotype-based matching to correct for population stratification in large-scale case-control genetic association studies

Weihua Guan, Liming Liang, Michael Boehnke, Gonçalo R. Abecasis

Research output: Contribution to journalArticlepeer-review

36 Scopus citations


Genome-wide association studies are helping to dissect the etiology of complex diseases. Although case-control association tests are generally more powerful than family-based association tests, population stratification can lead to spurious disease-marker association or mask a true association. Several methods have been proposed to match cases and controls prior to genotyping, using family information or epidemiological data, or using genotype data for a modest number of genetic markers. Here, we describe a genetic similarity score matching (GSM) method for efficient matched analysis of cases and controls in a genome-wide or large-scale candidate gene association study. GSM comprises three steps: (1) calculating similarity scores for pairs of individuals using the genotype data; (2) matching sets of cases and controls based on the similarity scores so that matched cases and controls have similar genetic background; and (3) using conditional logistic regression to perform association tests. Through computer simulation we show that GSM correctly controls false-positive rates and improves power to detect true disease predisposing variants. We compare GSM to genomic control using computer simulations, and find improved power using GSM. We suggest that initial matching of cases and controls prior to genotyping combined with careful re-matching after genotyping is a method of choice for genome-wide association studies.

Original languageEnglish (US)
Pages (from-to)508-517
Number of pages10
JournalGenetic epidemiology
Issue number6
StatePublished - 2009


  • Genetic similarity
  • Genome-wide association
  • Population stratification


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