Binomial mixture model-based association tests under genetic heterogeneity

Hui Zhou, Wei Pan

Research output: Contribution to journalArticlepeer-review

9 Scopus citations


Most of the existing association tests for population-based case-control studies are based on comparing the mean genotype scores between the case and control groups, which may not be efficient under genetic heterogeneity. Given that most common diseases are genetically heterogeneous, caused by mutations in multiple loci, it may be beneficial to fully account for genetic heterogeneity in an association test. Here we first propose a binomial mixture model for such a purpose and develop a corresponding mixture likelihood ratio test (MLRT) for a single locus. We also consider two methods to combine single-locus-based MLRTs across multiple loci in linkage disequilibrium to boost power when causal SNPs are not genotyped. We show with a wide spectrum of numerical examples that under genetic heterogeneity the proposed tests are more powerful than some commonly used association tests.

Original languageEnglish (US)
Pages (from-to)614-630
Number of pages17
JournalAnnals of Human Genetics
Issue number6
StatePublished - Nov 2009


  • Case-control study
  • EM algorithm
  • Genome-wide association study
  • Likelihood ratio test
  • Linkage disequilibrium (LD)
  • Mixture models
  • Permutation


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