Lastly, we extended our polygenic analyses to a drug naïve developmental sample (9–11 years of age at recruitment; analytic N=62 to 5,556). We concentrated on 12 traits that showed significant genetic correlations in the adult samples (Supplementary Table 38, Figure 6c). Although tobacco exposure was uncommon in this pediatric population (2.30% prevalence), externalizing behaviors, which emerge in childhood and are strong correlates of substance use, were available. After correcting for multiple testing, TUD PGS was significantly (p<4.00E-03) associated with externalizing behaviors (i.e., Child Behavior Check List [CBCL] externalizing scores, β=0.07, p=1.21E-06; CBCL ADHD scores, β=0.06, p=4.97E-05), as well as internalizing (i.e., suicide attempt, β=0.05, p=1.52E-03, CBCL depression scores, β=0.05, p=1.11E-03), cognitive ability (β=0.06, p=8.35E-06), neighborhood deprivation (β=0.04, p=1.05E-03), and weight-related phenotypes (i.e., BMI, β=0.06, p=1.61E-05; weight, β=0.04, p=2.77E-03). Notably, these children were not chronically exposed to tobacco; therefore, we would speculate that these associations are not a consequence of smoking but rather may underlie overlapping genetic architectures among the traits studied that predate use of tobacco.
