The Genetic Architecture of Differentiating Behavioral and Emotional Problems in Early Life

Early in life, behavioral and cognitive traits associated with risk for developing a psychiatric condition are broad and undifferentiated. As children develop, these traits differentiate into characteristic clusters of symptoms and behaviors that ultimately form the basis of diagnostic categories. Understanding this differentiation process-in the context of genetic risk for psychiatric conditions, which is highly generalized-can improve early detection and intervention.

We modeled the differentiation of behavioral and emotional problems from age 1.5 to 5 years (behavioral problems - emotional problems = differentiation score) in a preregistered study of ∼79,000 children from the population-based Norwegian Mother, Father, and Child Cohort Study. We used genomic structural equation modeling to identify genetic signal in differentiation and total problems, investigating their links with 11 psychiatric and neurodevelopmental conditions. We examined associations of polygenic scores (PGS) with both outcomes and assessed the relative contributions of direct and indirect genetic effects in ∼33,000 family trios.

Differentiation was primarily genetically correlated with psychiatric conditions via a neurodevelopmental factor. Total problems were primarily associated with the neurodevelopmental factor and p-factor. PGS analyses revealed an association between liability to attention-deficit/hyperactivity disorder and differentiation (β = 0.11; 95% CI, 0.10 to 0.12) and a weaker association with total problems (β = 0.06; 95% CI, 0.04 to 0.07). Trio-PGS analyses showed predominantly direct genetic effects on both outcomes.

We uncovered genomic signal in the differentiation process, mostly related to common variants associated with neurodevelopmental conditions. Investigating the differentiation of early-life behavioral and emotional problems may enhance our understanding of the developmental emergence of different psychiatric and neurodevelopmental conditions.