University of Oulu

Akingbuwa WA, Hammerschlag AR, Jami ES, et al. Genetic Associations Between Childhood Psychopathology and Adult Depression and Associated Traits in 42 998 Individuals: A Meta-analysis. JAMA Psychiatry. 2020;77(7):715–728. doi:10.1001/jamapsychiatry.2020.0527

Genetic associations between childhood psychopathology and adult depression and associated traits in 42 998 individuals : a meta-analysis

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Author: Akingbuwa, Wonuola A.1,2; Hammerschlag, Anke R.1,2,3; Jami, Eshim S.1,2;
Organizations: 1Vrije Univ Amsterdam, Dept Biol Psychol, Boechorststr 7, NL-1081 BT Amsterdam, Netherlands.
2Amsterdam Publ Hlth Res Inst, Amsterdam, Netherlands.
3Univ Queensland, Child Hlth Res Ctr, Brisbane, Qld, Australia.
4Kings Coll London, Inst Psychiat Psychol & Neurosci, Social Genet & Dev Psychiat Ctr, London, England.
5Imperial Coll London, Dept Epidemiol & Biostat, London, England.
6Univ Bristol, Sch Psychol Sci, Bristol, Avon, England.
7Univ Bristol, MRC Integrat Epidemiol Unit, Bristol, Avon, England.
8Univ Bristol, Ctr Acad Mental Hlth, Populat Hlth Sci, Bristol Med Sch, Bristol, Avon, England.
9Norwegian Inst Publ Hlth, Dept Mental Disorders, Oslo, Norway.
10Erasmus Univ, Child & Adolescent Psychiat, Med Ctr, Rotterdam, Netherlands.
11Lovisenberg Diaconal Hosp, Nic Waals Inst, Oslo, Norway.
12Qatar Fdn, Qatar Genome Programme, Doha, Qatar.
13Univ Med Ctr, Erasmus MC, Generat R Study Grp, Rotterdam, Netherlands.
14Univ Med Ctr Rotterdam, Dept Epidemiol, Erasmus MC, Rotterdam, Netherlands.
15Univ Med Ctr Rotterdam, Dept Internal Med, Erasmus MC, Rotterdam, Netherlands.
16South London & Maudsley Natl Hlth Serv Fdn Trust, Natl Inst Hlth Res, Biomed Res Ctr, London, England.
17Cardiff Univ, Med Res Council, Ctr Neuropsychiat Genet & Genom, Cardiff, Wales.
18Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
19Norwegian Inst Publ Hlth, Oslo, Norway.
20Univ Oslo, Oslo, Norway.
21Norwegian Inst Publ Hlth, Ctr Fertil & Hlth, Oslo, Norway.
22Univ Oslo, PROMENTA Res Ctr, Dept Psychol, Oslo, Norway.
23Imperial Coll London, Med Res Council, Publ Hlth England Ctr Environm & Hlth, London, England.
24Univ Oulu, Ctr Life Course Hlth Res, Oulu, Finland.
25Med Res Ctr Oulu, Oulu, Finland.
26Inst Biomed & Bioctr Oulu, Oulu, Finland.
27Brunel Univ, London Coll Hlth & Life Sci, Dept Life Sci, London, England.
28Univ Gothenburg, Gillberg Neuropsychiat Ctr, Ctr Eth Law & Mental Hlth, Gothenburg, Sweden.
29Univ Bristol, Natl Inst Hlth Res, Biomed Res Ctr, Univ Hosp Bristol Natl Hlth Serv Fdn Trust, Bristol, Avon, England.
30Harvard TH Chan Sch Med, Dept Social & Behav Sci, Boston, MA USA.
31Childrens Hlth Queensland Hosp & Hlth Serv, Child & Youth Mental Hlth Serv, Brisbane, Qld, Australia.
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 0.4 MB)
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Language: English
Published: American Medical Association, 2020
Publish Date: 2021-05-04


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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Series: JAMA psychiatry
ISSN: 2168-622X
ISSN-E: 2168-6238
ISSN-L: 2168-622X
Volume: 77
Issue: 7
Pages: 715 - 728
DOI: 10.1001/jamapsychiatry.2020.0527
Type of Publication: A1 Journal article – refereed
Field of Science: 3124 Neurology and psychiatry
Funding: This project has received funding from the European Union’s Horizon 2020 research and innovation programme, Marie Sklodowska Curie Actions (MSCA-ITN-2016) Innovative Training Networks (grant 721567 [Ms Akingbuwa, Dr Jami, Mrs Allegrini, Dr Karhunen, and Ms Diemer]). The Psychiatric Genomics Consortium has received major funding from the US National Institute of Mental Health and the US National Institute of Drug Abuse (grants U01 MH109528 and U01 MH1095320). Dr Hammerschlag is supported by the Children’s Hospital Foundation and University of Queensland strategic funding. Dr Sallis is a member of the MRC Integrative Epidemiology Unit at the University of Bristol (grant MC_UU_00011/7). Ms Askeland is supported by the Research Council of Norway (grant 274611). Dr Havdahl is supported by the South-Eastern Norway Regional Health Authority (grant 2018059) and is a member of the MRC Integrative Epidemiology Unit at the University of Bristol (grant MC_UU_00011/1). Dr Thapar is supported by the Wellcome Trust and MRC. Dr Boomsma is supported by Koninklijke Nederlandse Akademie van Wetenschappen Academy Professor Award (grant PAH/6635). Dr Reichborn-Kjennerud is supported by the Research Council of Norway (grant 274611). Dr Magnus is supported by the Research Council of Norway (grant 262700). Dr Rimfeld is funded by a Sir Henry Wellcome Postdoctoral Fellowship. Dr Ystrom is supported by the Research Council of Norway (grants 262177 and 288083). Mr Lundstrom is funded by the Child and Adolescent Twin Study in Sweden is supported by Swedish Research Council (Medicine, Humanities and Social Science, and SIMSAM), Funds under the ALF agreement, and the Swedish Research Council for Health, Working Life and Welfare (FORTE). Dr Munafò is a member of the MRC Integrative Epidemiology Unit at the University of Bristol (grant MC_UU_00011/7). Dr Plomin is supported by a Medical Research Council Professorship award (grant G19/2). Dr Tiemeier received funding from the Netherlands Organization for Health Research and Development (grant 016.VICI.170.200). Dr Nivard is supported by ZonMw (grants 531003014 and 849200011). Dr Bartels is funded by an ERC Consolidator Grant (WELL-BEING; grant 771057).
Copyright information: This is an open access article distributed under the terms of the CC-BY License. © 2020 Akingbuwa WA et al. JAMA Psychiatry.