The genetic architecture of differentiating behavioural and emotional problems in early life

Abstract

Abstract Early in life, behavioural 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 behaviours that ultimately form the basis of diagnostic categories. Understanding this differentiation process - in the context of genetic risk for psychiatric conditions, which is highly generalised - can improve early detection and treatment. We modelled the differentiation of behavioural and emotional problems from age 1.5-5 years (behavioural problems – emotional problems = differentiation score) in a pre-registered study of ~79 000 children from the population-based Norwegian Mother, Father, and Child Cohort Study. We used genomic structural equation modelling to identify genetic signal in differentiation and the total level of behavioural and emotional problems, investigating their links with 11 psychiatric and neurodevelopmental conditions. We examined associations of polygenic scores (PGS) with differentiation and total problems and assessed the relative contributions of direct and indirect genetic effects in over 33 000 family trios. Differentiation exhibited detectable common variant heritability (h2SNP = 0.023 [0.017, 0.029]), and was primarily genetically correlated with psychiatric conditions via a “neurodevelopmental” factor. PGS analyses revealed a substantial association between polygenic liability to ADHD and differentiation (β = 0.09 [0.08, 0.11]), and a weaker association with total problems (β = 0.05 [0.04, 0.06]). Trio-PGS analyses indicated predominantly direct genetic effects on both outcomes. We uncovered systematic genomic signal in the differentiation process, mostly related to common variants associated with neurodevelopmental conditions. Investigating the co-occurrence and differentiation of behavioural and emotional problems may enhance our ability to detect and eventually prevent the emergence of psychiatric conditions.