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Estimation of Linkage and Association from Allele Transmission Data
Author(s) -
Malley James D.,
Redner Richard A.,
Severini Thomas A.,
Badner Judith A.,
Pajevic Sinisa,
BaileyWilson Joan E.
Publication year - 2003
Publication title -
biometrical journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.108
H-Index - 63
eISSN - 1521-4036
pISSN - 0323-3847
DOI - 10.1002/bimj.200390017
Subject(s) - linkage disequilibrium , linkage (software) , statistics , transmission disequilibrium test , test statistic , mathematics , confidence interval , statistical hypothesis testing , genetic association , association (psychology) , identifiability , statistic , genetics , allele , haplotype , biology , psychology , genotype , single nucleotide polymorphism , psychotherapist , gene
The TDT provides a hypothesis test for the presence of linkage or association (linkage disequilibrium). However, since the TDT is a single test statistic, it cannot be used to separate association and linkage. The importance of this difficulty, following a significant TDT result, has been recently emphasized by Whittaker , Denham and Morris (2000), who alert the community to the possibility that a significant TDT may result from loose linkage and strong association, or from tight linkage and weak association. To attack this problem we start with the parametric model for family‐based allele transmission data of Sham and Curtis (1995) (or Sham (1998)) and find that the parameters in the model are not always identifiable. So we introduce a reparameterization that resolves the identifiability issues and leads to a valid likelihood ratio ( LR ) test for linkage. Since the linkage and association parameters are both of interest, we next introduce and apply an integrated likelihood ( IL ) approach to provide separate point estimates and confidence intervals for these parameters. The estimates are shown to have generally small bias and mean square error, while the confidence intervals have good average length and coverage probabilities. We compare the power of the IL approach for testing linkage and, separately association, with the TDT and LR .