Abstract
A combination of genetic and environmental factors working in interplay is thought to underlie
differences in symptoms of psychopathology between adolescents. Yet, studies that have investigated
gene-environment interaction in isolated aspects of developmental psychopathology lack robust
effects, highlighting the need for a broader approach. We adopted a multivariable framework to
investigate gene-environment interaction in internalising and externalising symptoms of
psychopathology in a sample of 3,337 16-year-olds from the Twins Early Development Study. We
used penalised regression models to examine the main effects of genetic factors (G), indexed by
combining 13 polygenic scores for psychopathology, and environmental factors (E), measured by
combining multiple environmental exposures during childhood and adolescence, on symptoms of
psychopathology. We also examined their additive effects (G+E) and their interaction (G×E).
Polygenic scores accounted for, on average, 2.7% of the variance in symptoms of psychopathology,
with stronger predictions for externalising symptoms, while environmental measures alone accounted
for an average of 7.1% of the variance. G+E accounted for an average of 9.1% of differences between
adolescents in symptoms of psychopathology. We observed small G×E effects for internalising
symptoms, accounting for an average of 1.1% of the variance. Children with a higher genetic risk
showed higher levels of internalising symptoms, especially when exposed to more chaos at home and
harsher parenting. Our findings indicate that genetic and environmental influences contribute
additively, underscoring the importance of jointly considering both factors to enhance our
understanding of youth psychopathology. At the same time, our results highlight the persistent
challenges involved in identifying robust G×E effects.
