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Extension of the generalized disequilibrium test to polytomous phenotypes and two-locus models.

Bureau A, Croteau J, Chagnon YC, Roy MA, Maziade M - Front Genet (2014)

Bottom Line: WE EXTEND THE USUAL LOGISTIC MODEL BETWEEN A DICHOTOMOUS PHENOTYPE AND AN ALLELE COUNT IN TWO WAYS: a polytomous phenotype with K > 2 levels, and modeling of allele counts at two unlinked marker loci.Simulations confirm that the tests have the expected statistical properties, and that their power exceeds that of the GDT under a favorable scenario.The score tests are illustrated with candidate genetic markers, a major psychosis phenotype and a cognitive endophenotype in large kindreds from Eastern Quebec.

View Article: PubMed Central - PubMed

Affiliation: Département de Médecine Sociale et Préventive, Université Laval Québec, QC, Canada ; Centre de Recherche de L'Institut Universitaire en Santé Mentale de Québec Québec, QC, Canada.

ABSTRACT
WE EXTEND THE USUAL LOGISTIC MODEL BETWEEN A DICHOTOMOUS PHENOTYPE AND AN ALLELE COUNT IN TWO WAYS: a polytomous phenotype with K > 2 levels, and modeling of allele counts at two unlinked marker loci. Inference is based on within-family information to guard against potential bias due to population genetic structure. Score tests of the model coefficients taking into account the correlation between relatives in entire pedigrees are derived as an extension of the Generalized Disequilibrium Test (GDT). Simulations confirm that the tests have the expected statistical properties, and that their power exceeds that of the GDT under a favorable scenario. The score tests are illustrated with candidate genetic markers, a major psychosis phenotype and a cognitive endophenotype in large kindreds from Eastern Quebec.

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Related in: MedlinePlus

Power of various within-family score tests to detect locus 2. See text for definitions of the acronyms of the tests. For tests conditional on another locus, subject pairs were weighted using expression 6.
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Figure 2: Power of various within-family score tests to detect locus 2. See text for definitions of the acronyms of the tests. For tests conditional on another locus, subject pairs were weighted using expression 6.

Mentions: Under the simulated scenario the endophenotype-to-disease model holds. While the test of the hypothesis 13 has some power, testing β33 = 0 (the interaction parameter for the combination of disease and endophenotype impairment) achieves the highest power among the tests considered (Figure 2). Using weight definition 7 instead of 6 led to nearly identical power (results not shown). Under this scenario, testing association for the same phenotypic category of the allele count at locus 2 β3(1L) = 0 or the entire vector = 0 does not provide a measurable power improvement over the GDT applied to the disease status in the subset of subjects with endophenotype impairment. Further comparisons of testing strategies under a variety of scenarios will be reported elsewhere.


Extension of the generalized disequilibrium test to polytomous phenotypes and two-locus models.

Bureau A, Croteau J, Chagnon YC, Roy MA, Maziade M - Front Genet (2014)

Power of various within-family score tests to detect locus 2. See text for definitions of the acronyms of the tests. For tests conditional on another locus, subject pairs were weighted using expression 6.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4126369&req=5

Figure 2: Power of various within-family score tests to detect locus 2. See text for definitions of the acronyms of the tests. For tests conditional on another locus, subject pairs were weighted using expression 6.
Mentions: Under the simulated scenario the endophenotype-to-disease model holds. While the test of the hypothesis 13 has some power, testing β33 = 0 (the interaction parameter for the combination of disease and endophenotype impairment) achieves the highest power among the tests considered (Figure 2). Using weight definition 7 instead of 6 led to nearly identical power (results not shown). Under this scenario, testing association for the same phenotypic category of the allele count at locus 2 β3(1L) = 0 or the entire vector = 0 does not provide a measurable power improvement over the GDT applied to the disease status in the subset of subjects with endophenotype impairment. Further comparisons of testing strategies under a variety of scenarios will be reported elsewhere.

Bottom Line: WE EXTEND THE USUAL LOGISTIC MODEL BETWEEN A DICHOTOMOUS PHENOTYPE AND AN ALLELE COUNT IN TWO WAYS: a polytomous phenotype with K > 2 levels, and modeling of allele counts at two unlinked marker loci.Simulations confirm that the tests have the expected statistical properties, and that their power exceeds that of the GDT under a favorable scenario.The score tests are illustrated with candidate genetic markers, a major psychosis phenotype and a cognitive endophenotype in large kindreds from Eastern Quebec.

View Article: PubMed Central - PubMed

Affiliation: Département de Médecine Sociale et Préventive, Université Laval Québec, QC, Canada ; Centre de Recherche de L'Institut Universitaire en Santé Mentale de Québec Québec, QC, Canada.

ABSTRACT
WE EXTEND THE USUAL LOGISTIC MODEL BETWEEN A DICHOTOMOUS PHENOTYPE AND AN ALLELE COUNT IN TWO WAYS: a polytomous phenotype with K > 2 levels, and modeling of allele counts at two unlinked marker loci. Inference is based on within-family information to guard against potential bias due to population genetic structure. Score tests of the model coefficients taking into account the correlation between relatives in entire pedigrees are derived as an extension of the Generalized Disequilibrium Test (GDT). Simulations confirm that the tests have the expected statistical properties, and that their power exceeds that of the GDT under a favorable scenario. The score tests are illustrated with candidate genetic markers, a major psychosis phenotype and a cognitive endophenotype in large kindreds from Eastern Quebec.

No MeSH data available.


Related in: MedlinePlus