ROBUST QUANTITATIVE TRAIT ASSOCIATION TESTS IN THE PARENT-OFFSPRING TRIAD DESIGN: CONDITIONAL LIKELIHOOD-BASED APPROACHES
Resource
ANNALS OF HUMAN GENETICS,73 PART 2,231-244.
Journal
Annals of Human Genetics
Pages
231-244
Date Issued
2009
Date
2009
Author(s)
王俊毅
戴政
Abstract
Association studies, based on either population data or familial data, have been widely applied to mapping of genes underlying complex diseases. In family-based association studies, using case-parent triad families, the popularly used transmission/disequilibrium test (TDT) was proposed for avoidance of spurious association results caused by other confounders such as population stratification. Originally, the TDT was developed for analysis of binary disease data. Extending it to allow for quantitative trait analysis of complex diseases and for robust analysis of binary diseases against the uncertainty of mode of inheritance has been thoroughly discussed. Nevertheless, studies on robust analysis of quantitative traits for complex diseases received relatively less attention. In this paper, we use parent-offspring triad families to demonstrate the feasibility of establishment of the robust candidate-gene association tests for quantitative traits. We first introduce the score statistics from the conditional likelihoods based on parent-offspring triad data under various genetic models. By applying two existing robust procedures we then construct the robust association tests for analysis of quantitative traits. Simulations are conducted to evaluate empirical type I error rates and powers of the proposed robust tests. The results show that these robust association tests do exhibit robustness against the effect of misspecification of the underlying genetic model on testing powers. ? Journal compilation ? 2009 Blackwell Publishing Ltd/University College London.
Subjects
Candidate-gene; Exponential family; Family-based association test; Mode of inheritance; Score test
SDGs
Other Subjects
article; dominant inheritance; gene frequency; gene linkage disequilibrium; genetic association; genotype; human; orthogonal rotation; priority journal; progeny; quantitative trait; quantitative trait locus; recessive inheritance; scoring system; statistical analysis; transmission disequilibrium test; Family; Genetic Techniques; Humans; Likelihood Functions; Models, Genetic; Parents
Type
journal article