Single Marker Family-Based Association Analysis Conditional on Parental Information

  • Ren-Hua Chung
  • Daniel D. Kinnamon
  • Eden R. Martin
Part of the Methods in Molecular Biology book series (MIMB, volume 1666)


Family-based designs have been commonly used in association studies. Different family structures such as extended pedigrees and nuclear families, including parent–offspring triads and families with multiple affected siblings (multiplex families), can be ascertained for family-based association analysis. Flexible association tests that can accommodate different family structures have been proposed. The pedigree disequilibrium test (PDT) (Martin et al., Am J Hum Genet 67:146–154, 2000) can use full genotype information from general (possibly extended) pedigrees with one or multiple affected siblings but requires parental genotypes or genotypes of unaffected siblings. On the other hand, the association in the presence of linkage (APL) test (Martin et al., Am J Hum Genet 73:1016–1026, 2003) is restricted to nuclear families with one or more affected siblings but can infer missing parental genotypes properly by accounting for identity-by-descent (IBD) parameters. Both the PDT and APL test are powerful association tests in the presence of linkage and can be used as complementary tools for association analysis. This chapter introduces these two tests and compares their properties. Recommendations and notes for performing the tests in practice are provided.

Key words

Family-based association test Linkage disequilibrium Transmission statistics Nontransmission statistics Parental information EM algorithm Rare variants Genome-wide association Extended pedigree Nuclear family Parallelization Population stratification 


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Copyright information

© Springer Science+Business Media LLC 2017

Authors and Affiliations

  • Ren-Hua Chung
    • 1
  • Daniel D. Kinnamon
    • 2
  • Eden R. Martin
    • 3
  1. 1.Division of Biostatistics and BioinformaticsInstitute of Population Health Sciences, National Health Research InstitutesNewyorkTaiwan
  2. 2.Division of Human Genetics, Department of Internal MedicineThe Ohio State University Wexner Medical CenterColumbusUSA
  3. 3.John P. Hussman Institute for Human Genomics, Leonard M. Miller School of MedicineUniversity of MiamiMiamiUSA

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