A method for using incomplete triads to test maternally mediated genetic effects and parent-of-origin effects in relation to a quantitative trait

Abstract

The authors recently developed a semiparametric family-based test for linkage and association between markers and quantitative traits. This quantitative polytomous logistic regression test allows for analysis of families with incomplete information on parental genotype. In addition, it is not necessary to assume normality of the quantitative trait. Previous simulations have shown that the new test is as powerful as the other widely used tests for linkage disequilibrium in relation to a quantitative trait. Here the authors propose an extension to quantitative polytomous logistic regression that allows testing for maternally mediated effects and parent-of-origin effects in the same framework. Missing data on parental genotype are accommodated through an expectation-maximization algorithm approach. Simulations show robustness of the new tests and good power for detecting effects in the presence or absence of offspring effects. Methods are illustrated with birth weight and gestational length, two quantitative outcomes for which data were collected in a Montreal, Canada, study of intrauterine growth restriction between May 1998 and June 2000. Copyright © 2005 by the Johns Hopkins Bloomberg School of Public Health. All rights reserved.