Multivariate analyses of molecular genetic associations between childhood psychopathology and adult mood disorders and related traits

Wonuola A. Akingbuwa*, Anke R. Hammerschlag, Andrea G. Allegrini, Hannah Sallis, Ralf Kuja-Halkola, Kaili Rimfeld, Paul Lichtenstein, Sebastian Lundstrom, Marcus R. Munafò, Robert Plomin, Michel G. Nivard, Meike Bartels, Christel M. Middeldorp

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Ubiquitous associations have been detected between different types of childhood psychopathology and polygenic risk scores based on adult psychiatric disorders and related adult outcomes, indicating that genetic factors partly explain the association between childhood psychopathology and adult outcomes. However, these analyses in general do not take into account the correlations between the adult trait and disorder polygenic risk scores. This study aimed to further clarify the influence of genetic factors on associations between childhood psychopathology and adult outcomes by accounting for these correlations. Using a multivariate multivariable regression, we analyzed associations of childhood attention-deficit/hyperactivity disorder (ADHD), internalizing, and social problems, with polygenic scores (PGS) of adult disorders and traits including major depression, bipolar disorder, subjective well-being, neuroticism, insomnia, educational attainment, and body mass index (BMI), derived for 20,539 children aged 8.5–10.5 years. After correcting for correlations between the adult phenotypes, major depression PGS were associated with all three childhood traits, that is, ADHD, internalizing, and social problems. In addition, BMI PGS were associated with ADHD symptoms and social problems, while neuroticism PGS were only associated with internalizing problems and educational attainment PGS were only associated with ADHD symptoms. PGS of bipolar disorder, subjective well-being, and insomnia were not associated with any childhood traits. Our findings suggest that associations between childhood psychopathology and adult traits like insomnia and subjective well-being may be primarily driven by genetic factors that influence adult major depression. Additionally, specific childhood phenotypes are genetically associated with educational attainment, BMI and neuroticism.

Original languageEnglish
Pages (from-to)3-12
Number of pages10
JournalAmerican Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
Issue number1-2
Publication statusPublished - 1 Jan 2023


  • childhood psychopathology
  • major depression
  • multivariate regression
  • polygenic scores

Cite this