Genetically Informed Regression Analysis: Application to Aggression Prediction by Inattention and Hyperactivity in Children and Adults

Dorret I Boomsma,Toos C E M Van Beijsterveldt,Michael C Neale,Conor V Dolan,Veronika V Odintsova

doi:10.1007/s10519-020-10025-9

Dorret I Boomsma, Toos C E M Van Beijsterveldt + Show 3 more

Open Access

https://doi.org/10.1007/s10519-020-10025-9

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Abstract

We present a procedure to simultaneously fit a genetic covariance structure model and a regression model to multivariate data from mono- and dizygotic twin pairs to test for the prediction of a dependent trait by multiple correlated predictors. We applied the model to aggressive behavior as an outcome trait and investigated the prediction of aggression from inattention (InA) and hyperactivity (HA) in two age groups. Predictions were examined in twins with an average age of 10 years (11,345 pairs), and in adult twins with an average age of 30 years (7433 pairs). All phenotypes were assessed by the same, but age-appropriate, instruments in children and adults. Because of the different genetic architecture of aggression, InA and HA, a model was fitted to these data that specified additive and non-additive genetic factors (A and D) plus common and unique environmental (C and E) influences. Given appropriate identifying constraints, this ADCE model is identified in trivariate data. We obtained different results for the prediction of aggression in children, where HA was the more important predictor, and in adults, where InA was the more important predictor. In children, about 36% of the total aggression variance was explained by the genetic and environmental components of HA and InA. Most of this was explained by the genetic components of HA and InA, i.e., 29.7%, with 22.6% due to the genetic component of HA. In adults, about 21% of the aggression variance was explained. Most was this was again explained by the genetic components of InA and HA (16.2%), with 8.6% due to the genetic component of InA.

Highlights

Multivariate extensions of the classical twin design, that rest on trait and cross-trait comparisons of resemblances in mono- and dizygotic (MZ and DZ) twins, allow for inferences regarding pleiotropy and correlated environmental effects (Martin and Eaves 1977), the direction of causation between correlated traits (Heath et al 1993; Duffy and Martin 1994), the moderation of genetic and environmental effects (Purcell 2002), and the analysis of the dimensionality of psychological instruments (Franić et al 2013)
Inattention and hyperactivity were assessed by a variety of instruments. They concluded that the strong, broad-sense, genetic effects on inattention and hyperactivity are substantially correlated, regardless of instrument or rater. When considering questions such as whether the association with aggression is stronger for inattention than for hyperactivity, we need to take into consideration that these two dimensions are not independent, e.g., there may be genetic pleiotropy, and that associations may differ across age groups
We applied the model to data from children and adults to address the question of differential prediction of aggression (Agg) by two components of attention deficithyperactivity disorder (ADHD), i.e. inattention (InA) and hyperactivity (HA)

Summary

Introduction

Multivariate extensions of the classical twin design, that rest on trait and cross-trait comparisons of resemblances in mono- and dizygotic (MZ and DZ) twins, allow for inferences regarding pleiotropy and correlated environmental effects (Martin and Eaves 1977), the direction of causation between correlated traits (Heath et al 1993; Duffy and Martin 1994), the moderation of genetic and environmental effects (Purcell 2002), and the analysis of the dimensionality of psychological (psychometric) instruments (Franić et al 2013). A comprehensive literature review and meta-analysis of studies in children, adolescents and adults on ADHD symptom dimensions indicated that aggressive behavior, and more generally externalizing disorders, are more strongly associated with hyperactivity/ impulsivity than with inattention (Willcutt et al 2012). When considering questions such as whether the association with aggression is stronger for inattention than for hyperactivity, we need to take into consideration that these two dimensions are not independent, e.g., there may be genetic pleiotropy, and that associations may differ across age groups In this contribution, we investigated the differences between inattention and hyperactivity as predictors of aggression in a genetic design, analyzing data from MZ and DZ twins

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