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Genetic associations between childhood psychopathology and adult depression and associated traits in 42 998 individuals

Akingbuwa, Wonuola A., Hammerschlag, Anke R., Jami, Eshim S., Allegrini, Andrea G., Karhunen, Ville, Sallis, Hannah, Ask, Helga, Askeland, Ragna B., Baselmans, Bart, Diemer, Elizabeth, Hagenbeek, Fiona A., Havdahl, Alexandra, Hottenga, Jouke-Jan, Mbarek, Hamdi, Rivadeneira, Fernando, Tesli, Martin, van Beijsterveldt, Catharina, Breen, Gerome, Lewis, Cathryn M., Thapar, Anita ORCID:, Boomsma, Dorret I., Kuja-Halkola, Ralf, Reichborn-Kjennerud, Ted, Magnus, Per, Rimfeld, Kaili, Ystrom, Eivind, Jarvelin, Marjo-Riitta, Lichtenstein, Paul, Lundstrom, Sebastian, Munafò, Marcus R., Plomin, Robert, Tiemeier, Henning, Nivard, Michel G., Bartels, Meike, Middeldorp, Christel M., Holmans, Peter A. ORCID:, Richards, Alexander L., Escott-Price, Valentina ORCID:, Forty, Liz, Fraser, Christine, Hamshere, Marian L. ORCID:, Craddock, Nicholas ORCID:, Jones, Ian, Kirov, George ORCID:, O'Donovan, Michael C. ORCID:, Owen, Michael J. ORCID:, Di Florio, Arianna ORCID:, Tansey, Katherine E. and The Bipolar Disorder and Major Depressive Disorder Working Group 2020. Genetic associations between childhood psychopathology and adult depression and associated traits in 42 998 individuals. JAMA Psychiatry 77 (7) , pp. 715-728. 10.1001/jamapsychiatry.2020.0527

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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 MeasuresRegression 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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Additional Information: The Cardiff University authors contributed to this paper as part of The Bipolar Disorder Working Group of the Psychiatric Genomics Consortium. This is an open access article distributed under the terms of the CC-BY License
Publisher: American Medical Association (AMA)
ISSN: 2168-622X
Date of First Compliant Deposit: 30 April 2020
Date of Acceptance: 17 February 2020
Last Modified: 11 Oct 2023 22:03

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