Abstract
Unlike case-control studies, family-based tests for association are protected against population stratification. Complex genetic traits are often governed by quantitative precursors and it has been argued that it may be a more powerful strategy to analyze these quantitative precursors instead of the clinical end point trait. Although methods have been developed for family-based association tests for single quantitative traits, it is of interest to develop such methods for multivariate phenotypes. We propose a novel transmission-based approach based on a trio design using a simple logistic regression to test for association with a multivariate phenotype. We use our proposed method to analyze data on systolic and diastolic blood pressure levels provided in Genetic Analysis Workshop 18. However, we find that the bivariate analysis of the two phenotypes did not provide more promising results compared to univariate analyses, suggesting a possibility of a different set of major genetic variants modulating the two phenotypes.
Highlights
The family-based design [1] for detecting association is a popular alternative to population-based case-control studies since it circumvents the problem of population stratification
Both the SBPand the diastolic blood pressure (DBP) levels were adjusted for these covariates for each time point and the tests for transmission disequilibrium were performed on the adjusted phenotypes
Because transmissions only from heterozygous parents are relevant for the proposed test for transmission disequilibrium, we analyze only those single-nucleotide polymorphism (SNP) that are made up of at least 25 informative trios for efficient estimation of parameters in the logistic regression
Summary
The family-based design [1] for detecting association is a popular alternative to population-based case-control studies since it circumvents the problem of population stratification. Because rare variants are likely to be more frequent in large families compared to the general population, it may be a more prudent strategy to test for transmission disequilibrium in pedigrees to identify these variants. We used smoking status and medication indicator (both defined as binary variables) at each time point of examination as covariates, as these factors could be potential confounders in the association analyses. Both the SBPand the DBP levels were adjusted for these covariates for each time point and the tests for transmission disequilibrium were performed on the adjusted phenotypes
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