Genotype-Based Association Test for General Pedigrees: The Genotype-PDT

Eden R. Martin, M. P. Bass, J. R. Gilbert, M. A. Pericak-Vance, E. R. Hauser

Research output: Contribution to journalArticlepeer-review

100 Scopus citations


Many family-based tests of linkage disequilibrium (LD) are based on counts of alleles rather than genotypes. However, allele-based tests may not detect interactions among alleles at a single locus that are apparent when examining associations with genotypes. Family-based tests of LD based on genotypes have been developed, but they are typically valid as tests of association only in families with a single affected individual. To take advantage of families with multiple affected individuals, we propose the genotype-pedigree disequilibrium test (geno-PDT) to test for LD between marker locus genotypes and disease. Unlike previous tests for genotypic association, the geno-PDT is valid in general pedigrees. Simulations to compare the power of the allele-based PDT and geno-PDT reveal that under an additive model, the allele-based PDT is more powerful, but that the geno-PDT can have greater power when the genetic model is recessive or dominant. Perhaps the most important property of the geno-PDT is the ability to test for association with particular genotypes, which can reveal underlying patterns of association at the genotypic level. These genotype-specific tests can be used to suggest possible underlying genetic models that are consistent with the pattern of genotypic association. This is illustrated through an application to a candidate gene analysis of the MLLT3 gene in families with Alzheimer disease. The geno-PDT approach for testing genotypes in general family data provides a useful tool for identifying genes in complex disease, and partitioning individual genotype contributions will help to dissect the influence of genotype on risk.

Original languageEnglish (US)
Pages (from-to)203-213
Number of pages11
JournalGenetic Epidemiology
Issue number3
StatePublished - Nov 2003
Externally publishedYes


  • Alzheimer disease
  • Family-based tests of association
  • Linkage disequilibrium

ASJC Scopus subject areas

  • Genetics(clinical)
  • Epidemiology


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