<p class="first" id="P1">Research using twins has found that much of the variability
in externalizing phenotypes
– including alcohol and drug use, impulsive personality traits, risky sex and property
crime – is explained by genetic factors. Nevertheless, identification of specific
genes and variants associated with these traits has proven to be difficult, likely
because individual differences in externalizing are explained by many genes of small
individual effect. Moreover, twin research indicates that heritable variance in externalizing
behaviors is mostly shared across the externalizing spectrum rather than specific
to any behavior. We use a longitudinal, “deep phenotyping” approach to model a general
externalizing factor reflecting persistent engagement in a variety of socially problematic
behaviors measured at eleven assessment occasions spanning early adulthood (ages 18
to 28). In an ancestrally homogenous sample of non-Hispanic Whites (
<i>N</i> = 337), we then tested for enrichment of associations between the persistent
externalizing
factor and a set of 3,281 polymorphisms within 104 genes that were previously identified
as associated with alcohol-use behaviors. Next we tested for enrichment among domain-specific
factors (e.g., property crime) composed of residual variance not accounted for by
the common factor. Significance was determined relative to bootstrapped empirical
thresholds derived from permutations of phenotypic data. Results indicated significant
enrichment of genetic associations for persistent externalizing, but not for domain-specific
factors. Consistent with twin research findings, these results suggest that genetic
variants are broadly associated with externalizing behaviors rather than unique to
specific behaviors.
</p><div class="section">
<a class="named-anchor" id="S1">
<!--
named anchor
-->
</a>
<h5 class="section-title" id="d5140473e124">General Scientific Summary</h5>
<p id="P2">This study shows that variation in 104 genes is associated with socially
problematic
“externalizing” behavior, including substance misuse, property crime, risky sex, and
aspects of impulsive personality. Importantly, this association was with the common
variation across these behaviors rather than with the variation unique to any given
behavior. The manuscript demonstrates a potentially advantageous technique for relating
sets of hypothesized genes to complex traits or behaviors.
</p>
</div>