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

doi:10.1002/ajmg.b.32922

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

Am J Med Genet B Neuropsychiatr Genet. 2023 Jan;192(1-2):3-12. doi: 10.1002/ajmg.b.32922. Epub 2022 Nov 15.

Authors

Wonuola A Akingbuwa^{1

2}, Anke R Hammerschlag^{1

2

3}, Andrea G Allegrini^{4

5}, Hannah Sallis^{6

7

8}, Ralf Kuja-Halkola⁹, Kaili Rimfeld⁴, Paul Lichtenstein⁹, Sebastian Lundstrom¹⁰, Marcus R Munafò^{6

7

11}, Robert Plomin⁴, Michel G Nivard¹, Meike Bartels^{1

2}, Christel M Middeldorp^{1

3

12}

Affiliations

¹ Department of Biological Psychology, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
² Amsterdam Public Health Research Institute, Amsterdam, The Netherlands.
³ Child Health Research Centre, the University of Queensland, Brisbane, Queensland, Australia.
⁴ Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
⁵ Division of Psychology and Language Sciences, Department of Clinical, Educational and Health Psychology, University College London, London, UK.
⁶ School of Psychological Science, University of Bristol, Bristol, UK.
⁷ MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK.
⁸ Centre for Academic Mental Health, Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.
⁹ Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
¹⁰ Centre for Ethics Law and Mental Health, Gillberg Neuropsychiatry Centre, University of Gothenburg, Gothenburg, Sweden.
¹¹ NIHR Biomedical Research Centre, University Hospitals Bristol NHS Foundation Trust, University of Bristol, Bristol, UK.
¹² Child and Youth Mental Health Service, Children's Health Queensland Hospital and Health Services, Brisbane, Queensland, Australia.

Abstract

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.

Keywords: childhood psychopathology; major depression; multivariate regression; polygenic scores.

MeSH terms

Attention Deficit Disorder with Hyperactivity* / genetics
Attention Deficit Disorder with Hyperactivity* / psychology
Depressive Disorder, Major* / genetics
Genome-Wide Association Study
Humans
Molecular Biology
Multifactorial Inheritance / genetics
Multivariate Analysis
Psychopathology

Abstract

MeSH terms

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