A generalized Defries-Fulker regression framework for the analysis of twin data

Abstract

Twin studies compare the similarity between monozygotic twins to that between dizygotic twins in order to investigate the relative contributions of latent genetic and environmental factors influencing a phenotype. Statistical methods for twin data include likelihood estimation and Defries-Fulker regression. We propose a new generalization of the Defries-Fulker model that fully incorporates the effects of observed covariates on both members of a twin pair and is robust to violations of the Normality assumption. A simulation study demonstrates that the method is competitive with likelihood analysis. The Defries-Fulker strategy yields new insight into the parameter space of the twin model and provides a novel, prediction-based interpretation of twin study results that unifies continuous and binary traits. Due to the simplicity of its structure, extensions of the model have the potential to encompass generalized linear models, censored and truncated data; and gene by environment interactions.

Figure 1. The ACDE triangle

The horizontal and vertical axes are constraints that are part of the classical ACDE model, which assumes non-negativity of the variance components.

Figure 2

Alternative interpretatons of γ_MZ > 2 γ_DZ.

Figure 3. Screen snapshot of BPD analysis

Command line and output from Stata results window for the full two-parameter GDF model of BPD risk, using a binomial GLM, with quadratic effect of gestational age. Displayed p-values are two-sided.