New research
No Genetic Influence for Childhood Behavior Problems From DNA Analysis

https://doi.org/10.1016/j.jaac.2013.07.016Get rights and content
Under a Creative Commons license
open access

Objective

Twin studies of behavior problems in childhood point to substantial genetic influence. It is now possible to estimate genetic influence using DNA alone in samples of unrelated individuals, not relying on family-based designs such as twins. A linear mixed model, which incorporates DNA microarray data, has confirmed twin results by showing substantial genetic influence for diverse traits in adults. Here we present direct comparisons between twin and DNA heritability estimates for childhood behavior problems as rated by parents, teachers, and children themselves.

Method

Behavior problem data from 2,500 UK-representative 12-year-old twin pairs were used in twin analyses; DNA analyses were based on 1 member of the twin pair with genotype data for 1.7 million DNA markers. Diverse behavior problems were assessed, including autistic, depressive, and hyperactive symptoms. Genetic influence from DNA was estimated using genome-wide complex trait analysis (GCTA), and the twin estimates of heritability were based on standard twin model fitting.

Results

Behavior problems in childhood—whether rated by parents, teachers, or children themselves—show no significant genetic influence using GCTA, even though twin study estimates of heritability are substantial in the same sample, and even though both GCTA and twin study estimates of genetic influence are substantial for cognitive and anthropometric traits.

Conclusions

We suggest that this new type of “missing heritability,” that is, the gap between GCTA and twin study estimates for behavior problems in childhood, is due to nonadditive genetic influence, which will make it more difficult to identify genes responsible for heritability.

Key Words

behavior problems
cognitive abilities
genome-wide complex trait analysis (GCTA)
heritability
twin study

Cited by (0)

This article is discussed in an editorial by Dr. Stephen V. Faraone on page 1006.

The Twins Early Development Study (TEDS) is supported by a program grant to Dr. Plomin from the UK Medical Research Council (G0901245, and previously G0500079), with additional support from the US National Institutes of Health (HD044454; HD059215). Genome-wide genotyping was made possible by a grant from the Wellcome Trust to the Wellcome Trust Case Control Consortium 2 project (085475/B/08/Z; 085475/Z/08/Z). Dr. Plomin is supported by a Medical Research Council Research Professorship award (G19/2) and a European Advanced Investigator award (295366). Mr. Trzaskowski is supported by a Medical Research Council studentship.

Dr. Trzaskowski served as the statistical expert for this research. He had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

The authors thank the reviewers for highlighting several valuable issues.

Disclosure: Drs. Dale, Plomin, and Trzaskowksi report no biomedical financial interests or potential conflicts of interest.