Our mediation analysis shows that both externalising behaviours and cognitive ability in childhood partially mediate the direct genetic effects of multiple PGIs and of deleterious rare variants on adolescent mental health symptoms - identifying childhood as a potential window for intervention.

Our findings support existing evidence that associations between externalising symptoms and PGIs for externalising behaviours, ADHD, and the cognitive component of educational attainment are primarily explained by direct genetic effects.

I’m most excited about our rare variant findings: a higher burden of deleterious protein-truncating variants is associated with increased mental health symptoms. Trio models indicated direct genetic effects on externalising in MCS and on internalising symptoms in ALSPAC.

9/ The presence of a diagnostic genetic variant modifies the relationship between polygenic predisposition to education-related traits and gestational duration, suggesting that the nature of the diagnostic variant has the largest impact on risk of preterm delivery.

7/ Both preterm and term probands are enriched for pathogenic de novo mutations. However, the fraction of cases explained by DNMs in known DD-associated genes is higher in term than preterm cases, while DNMs in as-yet-undiscovered genes contribute approximately equally to both groups.

5/ One of the key findings is that prematurity and diagnostic genetic variants act additively and independently to influence phenotypic severity in developmental disorders. Premature probands have more affected organ systems and delayed developmental milestone attainment compared to term probands.