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

Adrian Dahl Askelund; Laura Hegemann; Andrea G Allegrini; Elizabeth C Corfield; Helga Ask; Neil M Davies; Ole A Andreassen; Alexandra Havdahl; Laurie J Hannigan

doi:10.1016/j.biopsych.2024.12.021

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

Biol Psychiatry. 2025 Jan 8:S0006-3223(25)00022-8. doi: 10.1016/j.biopsych.2024.12.021. Online ahead of print.

Authors

Adrian Dahl Askelund¹, Laura Hegemann², Andrea G Allegrini³, Elizabeth C Corfield⁴, Helga Ask⁵, Neil M Davies⁶, Ole A Andreassen⁷, Alexandra Havdahl⁸, Laurie J Hannigan⁹

Affiliations

¹ PsychGen Center for Genetic Epidemiology and Mental Health, Norwegian Institute of Public Health, Oslo, Norway; Psychiatric Genetic Epidemiology group, Research Department, Lovisenberg Diaconal Hospital, Oslo, Norway. Electronic address: [email protected].
² PsychGen Center for Genetic Epidemiology and Mental Health, Norwegian Institute of Public Health, Oslo, Norway; Psychiatric Genetic Epidemiology group, Research Department, Lovisenberg Diaconal Hospital, Oslo, Norway. Electronic address: [email protected].
³ Division of Psychology and Language Sciences, Department of Clinical, Educational and Health Psychology, University College London, London, UK; Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK. Electronic address: [email protected].
⁴ PsychGen Center for Genetic Epidemiology and Mental Health, Norwegian Institute of Public Health, Oslo, Norway; Psychiatric Genetic Epidemiology group, Research Department, Lovisenberg Diaconal Hospital, Oslo, Norway. Electronic address: [email protected].
⁵ PsychGen Center for Genetic Epidemiology and Mental Health, Norwegian Institute of Public Health, Oslo, Norway; Department of Psychology, University of Oslo, Oslo, Norway. Electronic address: [email protected].
⁶ MRC Integrative Epidemiology Unit, Bristol Medical School, University of Bristol, Bristol, UK; Division of Psychiatry, University College London, United Kingdom; Department of Statistical Sciences, University College London, London WC1E 6BT, UK; K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Norway. Electronic address: [email protected].
⁷ NORMENT Centre, Institute of Clinical Medicine, University of Oslo and Division of Mental Health and Addiction, Oslo University Hospital, 0407 Oslo, Norway; KG Jebsen Centre for Neurodevelopmental disorders, University of Oslo, Oslo, Norway. Electronic address: [email protected].
⁸ PsychGen Center for Genetic Epidemiology and Mental Health, Norwegian Institute of Public Health, Oslo, Norway; Psychiatric Genetic Epidemiology group, Research Department, Lovisenberg Diaconal Hospital, Oslo, Norway; Department of Psychology, University of Oslo, Oslo, Norway; MRC Integrative Epidemiology Unit, Bristol Medical School, University of Bristol, Bristol, UK. Electronic address: [email protected].
⁹ PsychGen Center for Genetic Epidemiology and Mental Health, Norwegian Institute of Public Health, Oslo, Norway; Psychiatric Genetic Epidemiology group, Research Department, Lovisenberg Diaconal Hospital, Oslo, Norway; MRC Integrative Epidemiology Unit, Bristol Medical School, University of Bristol, Bristol, UK. Electronic address: [email protected].

PMID: 39793691
DOI: 10.1016/j.biopsych.2024.12.021

Abstract

Background: 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.

Methods: We modeled the differentiation of behavioral and emotional problems from age 1.5-5 years (behavioral 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 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.

Results: 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 ADHD and differentiation (β=0.11 [0.10,0.12]), and a weaker association with total problems (β=0.06 [0.04,0.07]). Trio-PGS analyses showed predominantly direct genetic effects on both outcomes.

Conclusions: 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.

Keywords: attention-deficit/hyperactivity disorder; behavioral problems; differentiation; emotional problems; genomic structural equation modeling; trio polygenic score.