Genetic Associations Between Childhood Psychopathology and Adult Depression and Associated Traits in 42 998 Individuals: A Meta-analysis | Attention Deficit/Hyperactivity Disorders | JAMA Psychiatry | JAMA Network
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    Original Investigation
    April 15, 2020

    Genetic Associations Between Childhood Psychopathology and Adult Depression and Associated Traits in 42 998 Individuals: A Meta-analysis

    Author Affiliations
    • 1Department of Biological Psychology, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands
    • 2Amsterdam Public Health Research Institute, Amsterdam, the Netherlands
    • 3Child Health Research Centre, The University of Queensland, Brisbane, Queensland, Australia
    • 4Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, United Kingdom
    • 5Department of Epidemiology and Biostatistics, Imperial College London, London, United Kingdom
    • 6University of Bristol School of Psychological Science, Bristol, United Kingdom
    • 7MRC Integrative Epidemiology Unit, University of Bristol, Bristol, United Kingdom
    • 8Centre for Academic Mental Health, Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom
    • 9Department of Mental Disorders, Norwegian Institute of Public Health, Oslo, Norway
    • 10Child and Adolescent Psychiatry, Erasmus University Medical Center, Rotterdam, the Netherlands
    • 11Nic Waals Institute, Lovisenberg Diaconal Hospital, Oslo, Norway
    • 12Department of Mental Disorders, Norwegian Institute of Public Health, Oslo, Norway
    • 13Qatar Genome Programme, Qatar Foundation, Doha, Qatar
    • 14The Generation R Study Group, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands
    • 15Erasmus MC, Department of Epidemiology, University Medical Center Rotterdam, Rotterdam, the Netherlands
    • 16Erasmus MC, Department of Internal Medicine, University Medical Center Rotterdam, Rotterdam, the Netherlands
    • 17National Institute of Health Research Biomedical Research Centre, South London and Maudsley National Health Services Foundation Trust, London, London, United Kingdom
    • 18Medical Research Council Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, United Kingdom
    • 19Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
    • 20Norwegian Institute of Public Health, Oslo, Norway
    • 21University of Oslo, Oslo, Norway
    • 22Centre for Fertility and Health, Norwegian Institute of Public Health, Oslo, Norway
    • 23PROMENTA Research Center, Department of Psychology, University of Oslo, Oslo, Norway
    • 24Medical Research Council–Public Health England Centre for Environment and Health, Imperial College London, London, United Kingdom
    • 25Center for Life Course Health Research, University of Oulu, Oulu, Finland
    • 26Medical Research Center Oulu, Oulu, Finland
    • 27Institute of Biomedicine and Biocenter of Oulu, Oulu, Finland
    • 28Department of Life Sciences, Brunel University London College of Health and Life Sciences, London, United Kingdom
    • 29Centre for Ethics Law and Mental Health, Gillberg Neuropsychiatry Centre, University of Gothenburg, Gothenburg, Sweden
    • 30National Institute of Health Research Biomedical Research Centre, University Hospitals Bristol National Health Services Foundation Trust, University of Bristol, Bristol, United Kingdom
    • 31Department of Social and Behavioral Science, Harvard T. H. Chan School of Medicine, Boston, Massachusetts
    • 32Child and Youth Mental Health Service, Children's Health Queensland Hospital and Health Services, Brisbane, Queensland, Australia
    JAMA Psychiatry. 2020;77(7):715-728. doi:10.1001/jamapsychiatry.2020.0527
    Key Points

    Question  Do genetic factors underlie the association between childhood psychopathology and adult mood disorders and associated traits?

    Findings  This meta-analysis of longitudinal cohorts, which includes data on 42 998 participants, revealed significant associations between childhood psychopathology and adult polygenic scores of major depression, subjective well-being, neuroticism, insomnia, educational attainment, and body mass index but not bipolar disorder.

    Meaning  Per this analysis, shared genetic factors exist between childhood psychopathology traits from age 6 years onwards and adult depression and associated traits.

    Abstract

    Importance  Adult mood disorders are often preceded by behavioral and emotional problems in childhood. It is yet unclear what explains the associations between childhood psychopathology and adult traits.

    Objective  To investigate whether genetic risk for adult mood disorders and associated traits is associated with childhood disorders.

    Design, Setting, and Participants  This meta-analysis examined data from 7 ongoing longitudinal birth and childhood cohorts from the UK, the Netherlands, Sweden, Norway, and Finland. Starting points of data collection ranged from July 1985 to April 2002. Participants were repeatedly assessed for childhood psychopathology from ages 6 to 17 years. Data analysis occurred from September 2017 to May 2019.

    Exposures  Individual polygenic scores (PGS) were constructed in children based on genome-wide association studies of adult major depression, bipolar disorder, subjective well-being, neuroticism, insomnia, educational attainment, and body mass index (BMI).

    Main Outcomes and Measures  Regression meta-analyses were used to test associations between PGS and attention-deficit/hyperactivity disorder (ADHD) symptoms and internalizing and social problems measured repeatedly across childhood and adolescence and whether these associations depended on childhood phenotype, age, and rater.

    Results  The sample included 42 998 participants aged 6 to 17 years. Male participants varied from 43.0% (1040 of 2417 participants) to 53.1% (2434 of 4583 participants) by age and across all cohorts. The PGS of adult major depression, neuroticism, BMI, and insomnia were positively associated with childhood psychopathology (β estimate range, 0.023-0.042 [95% CI, 0.017–0.049]), while associations with PGS of subjective well-being and educational attainment were negative (β, −0.026 to −0.046 [95% CI, −0.020 to −0.057]). There was no moderation of age, type of childhood phenotype, or rater with the associations. The exceptions were stronger associations between educational attainment PGS and ADHD compared with internalizing problems (Δβ, 0.0561 [Δ95% CI, 0.0318-0.0804]; ΔSE, 0.0124) and social problems (Δβ, 0.0528 [Δ95% CI, 0.0282-0.0775]; ΔSE, 0.0126), and between BMI PGS and ADHD and social problems (Δβ, −0.0001 [Δ95% CI, −0.0102 to 0.0100]; ΔSE, 0.0052), compared with internalizing problems (Δβ, −0.0310 [Δ95% CI, −0.0456 to −0.0164]; ΔSE, 0.0074). Furthermore, the association between educational attainment PGS and ADHD increased with age (Δβ, −0.0032 [Δ 95% CI, −0.0048 to −0.0017]; ΔSE, 0.0008).

    Conclusions and Relevance  Results from this study suggest the existence of a set of genetic factors influencing a range of traits across the life span with stable associations present throughout childhood. Knowledge of underlying mechanisms may affect treatment and long-term outcomes of individuals with psychopathology.

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