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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Kim-Cohen  J, Caspi  A, Moffitt  TE, Harrington  H, Milne  BJ, Poulton  R.  Prior juvenile diagnoses in adults with mental disorder: developmental follow-back of a prospective-longitudinal cohort.   Arch Gen Psychiatry. 2003;60(7):709-717. doi:10.1001/archpsyc.60.7.709PubMedGoogle ScholarCrossref
Rao  U, Chen  L-A.  Characteristics, correlates, and outcomes of childhood and adolescent depressive disorders.   Dialogues Clin Neurosci. 2009;11(1):45-62.PubMedGoogle Scholar
Biederman  J, Ball  SW, Monuteaux  MC,  et al.  New insights into the comorbidity between ADHD and major depression in adolescent and young adult females.   J Am Acad Child Adolesc Psychiatry. 2008;47(4):426-434. doi:10.1097/CHI.0b013e31816429d3PubMedGoogle ScholarCrossref
Meinzer  MC, Lewinsohn  PM, Pettit  JW,  et al.  Attention-deficit/hyperactivity disorder in adolescence predicts onset of major depressive disorder through early adulthood.   Depress Anxiety. 2013;30(6):546-553. doi:10.1002/da.22082PubMedGoogle ScholarCrossref
Loth  AK, Drabick  DA, Leibenluft  E, Hulvershorn  LA.  Do childhood externalizing disorders predict adult depression? a meta-analysis.   J Abnorm Child Psychol. 2014;42(7):1103-1113. doi:10.1007/s10802-014-9867-8PubMedGoogle ScholarCrossref
Erickson  J, El-Gabalawy  R, Palitsky  D,  et al.  Educational attainment as a protective factor for psychiatric disorders: findings from a nationally representative longitudinal study.   Depress Anxiety. 2016;33(11):1013-1022. doi:10.1002/da.22515PubMedGoogle ScholarCrossref
Polderman  TJC, Boomsma  DI, Bartels  M, Verhulst  FC, Huizink  AC.  A systematic review of prospective studies on attention problems and academic achievement.   Acta Psychiatr Scand. 2010;122(4):271-284. doi:10.1111/j.1600-0447.2010.01568.xPubMedGoogle ScholarCrossref
Breslau  J, Lane  M, Sampson  N, Kessler  RC.  Mental disorders and subsequent educational attainment in a US national sample.   J Psychiatr Res. 2008;42(9):708-716. doi:10.1016/j.jpsychires.2008.01.016PubMedGoogle ScholarCrossref
Costello  EJ, Maughan  B.  Annual research review: Optimal outcomes of child and adolescent mental illness.   J Child Psychol Psychiatry. 2015;56(3):324-341. doi:10.1111/jcpp.12371PubMedGoogle ScholarCrossref
Riemann  D.  Insomnia and comorbid psychiatric disorders.   Sleep Med. 2007;8(suppl 4):S15-S20. doi:10.1016/S1389-9457(08)70004-2PubMedGoogle ScholarCrossref
Goldman-Mellor  S, Gregory  AM, Caspi  A,  et al.  Mental health antecedents of early midlife insomnia: evidence from a four-decade longitudinal study.   Sleep. 2014;37(11):1767-1775. doi:10.5665/sleep.4168PubMedGoogle ScholarCrossref
Bartels  M, Cacioppo  JT, van Beijsterveldt  TC, Boomsma  DI.  Exploring the association between well-being and psychopathology in adolescents.   Behav Genet. 2013;43(3):177-190. doi:10.1007/s10519-013-9589-7PubMedGoogle ScholarCrossref
Kendler  KS, Gatz  M, Gardner  CO, Pedersen  NL.  Personality and major depression: a Swedish longitudinal, population-based twin study.   Arch Gen Psychiatry. 2006;63(10):1113-1120. doi:10.1001/archpsyc.63.10.1113PubMedGoogle ScholarCrossref
Rosenström  T, Gjerde  LC, Krueger  RF,  et al.  Joint factorial structure of psychopathology and personality.   Psychol Med. 2019;49(13):2158-2167.PubMedGoogle ScholarCrossref
Aldinger  M, Stopsack  M, Ulrich  I,  et al.  Neuroticism developmental courses—implications for depression, anxiety and everyday emotional experience; a prospective study from adolescence to young adulthood.   BMC Psychiatry. 2014;14(1):210. doi:10.1186/s12888-014-0210-2PubMedGoogle ScholarCrossref
Newton-Howes  G, Horwood  J, Mulder  R.  Personality characteristics in childhood and outcomes in adulthood: findings from a 30 year longitudinal study.   Aust N Z J Psychiatry. 2015;49(4):377-386. doi:10.1177/0004867415569796PubMedGoogle ScholarCrossref
Hasler  G, Pine  DS, Gamma  A,  et al.  The associations between psychopathology and being overweight: a 20-year prospective study.   Psychol Med. 2004;34(6):1047-1057. doi:10.1017/S0033291703001697PubMedGoogle ScholarCrossref
Anderson  SE, Cohen  P, Naumova  EN, Must  A.  Association of depression and anxiety disorders with weight change in a prospective community-based study of children followed up into adulthood.   Arch Pediatr Adolesc Med. 2006;160(3):285-291. doi:10.1001/archpedi.160.3.285PubMedGoogle ScholarCrossref
Fuemmeler  BF, Østbye  T, Yang  C, McClernon  FJ, Kollins  SH.  Association between attention-deficit/hyperactivity disorder symptoms and obesity and hypertension in early adulthood: a population-based study.   Int J Obes (Lond). 2011;35(6):852-862. doi:10.1038/ijo.2010.214PubMedGoogle ScholarCrossref
Polderman  TJC, Benyamin  B, de Leeuw  CA,  et al.  Meta-analysis of the heritability of human traits based on fifty years of twin studies.   Nat Genet. 2015;47(7):702-709. doi:10.1038/ng.3285PubMedGoogle ScholarCrossref
Anttila  V, Bulik-Sullivan  B, Finucane  HK,  et al; Brainstorm Consortium.  Analysis of shared heritability in common disorders of the brain.   Science. 2018;360(6395):eaap8757. doi:10.1126/science.aap8757PubMedGoogle Scholar
Jansen  PR, Watanabe  K, Stringer  S,  et al; 23andMe Research Team.  Genome-wide analysis of insomnia in 1,331,010 individuals identifies new risk loci and functional pathways.   Nat Genet. 2019;51(3):394-403. doi:10.1038/s41588-018-0333-3PubMedGoogle ScholarCrossref
Kan  K-J, Dolan  CV, Nivard  MG,  et al.  Genetic and environmental stability in attention problems across the lifespan: evidence from the Netherlands twin register.   J Am Acad Child Adolesc Psychiatry. 2013;52(1):12-25. doi:10.1016/j.jaac.2012.10.009PubMedGoogle ScholarCrossref
Nivard  MG, Dolan  CV, Kendler  KS,  et al.  Stability in symptoms of anxiety and depression as a function of genotype and environment: a longitudinal twin study from ages 3 to 63 years.   Psychol Med. 2015;45(5):1039-1049. doi:10.1017/S003329171400213XPubMedGoogle ScholarCrossref
Cheesman  R, Purves  KL, Pingault  J-B,  et al; Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium.  Extracting stability increases the SNP heritability of emotional problems in young people.   Transl Psychiatry. 2018;8(1):223. doi:10.1038/s41398-018-0269-5PubMedGoogle ScholarCrossref
Birmaher  B, Axelson  D, Goldstein  B,  et al.  Psychiatric disorders in preschool offspring of parents with bipolar disorder: the Pittsburgh Bipolar Offspring Study (BIOS).   Am J Psychiatry. 2010;167(3):321-330. doi:10.1176/appi.ajp.2009.09070977PubMedGoogle ScholarCrossref
Hillegers  MH, Reichart  CG, Wals  M, Verhulst  FC, Ormel  J, Nolen  WA.  Five-year prospective outcome of psychopathology in the adolescent offspring of bipolar parents.   Bipolar Disord. 2005;7(4):344-350. doi:10.1111/j.1399-5618.2005.00215.xPubMedGoogle ScholarCrossref
Mesman  E, Nolen  WA, Reichart  CG, Wals  M, Hillegers  MH.  The Dutch bipolar offspring study: 12-year follow-up.   Am J Psychiatry. 2013;170(5):542-549. doi:10.1176/appi.ajp.2012.12030401PubMedGoogle ScholarCrossref
Wray  NR, Lee  SH, Mehta  D, Vinkhuyzen  AA, Dudbridge  F, Middeldorp  CM.  Research review: polygenic methods and their application to psychiatric traits.   J Child Psychol Psychiatry. 2014;55(10):1068-1087. doi:10.1111/jcpp.12295PubMedGoogle ScholarCrossref
Krapohl  E, Euesden  J, Zabaneh  D,  et al.  Phenome-wide analysis of genome-wide polygenic scores.   Mol Psychiatry. 2016;21(9):1188-1193. doi:10.1038/mp.2015.126PubMedGoogle ScholarCrossref
Riglin  L, Collishaw  S, Richards  A,  et al.  The impact of schizophrenia and mood disorder risk alleles on emotional problems: investigating change from childhood to middle age.   Psychol Med. 2018;48(13):2153-2158.PubMedGoogle ScholarCrossref
Jansen  PR, Polderman  TJC, Bolhuis  K,  et al.  Polygenic scores for schizophrenia and educational attainment are associated with behavioural problems in early childhood in the general population.   J Child Psychol Psychiatry. 2018;59(1):39-47. doi:10.1111/jcpp.12759PubMedGoogle ScholarCrossref
de Zeeuw  EL, van Beijsterveldt  CE, Glasner  TJ,  et al; Social Science Genetic Association Consortium.  Polygenic scores associated with educational attainment in adults predict educational achievement and ADHD symptoms in children.   Am J Med Genet B Neuropsychiatr Genet. 2014;165B(6):510-520. doi:10.1002/ajmg.b.32254PubMedGoogle ScholarCrossref
Stergiakouli  E, Martin  J, Hamshere  ML,  et al.  Association between polygenic risk scores for attention-deficit hyperactivity disorder and educational and cognitive outcomes in the general population.   Int J Epidemiol. 2017;46(2):421-428.PubMedGoogle Scholar
Wray  NR, Ripke  S, Mattheisen  M,  et al; eQTLGen; 23andMe; Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium.  Genome-wide association analyses identify 44 risk variants and refine the genetic architecture of major depression.   Nat Genet. 2018;50(5):668-681. doi:10.1038/s41588-018-0090-3PubMedGoogle ScholarCrossref
Howard  DM, Adams  MJ, Clarke  T-K,  et al; 23andMe Research Team; Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium.  Genome-wide meta-analysis of depression identifies 102 independent variants and highlights the importance of the prefrontal brain regions.   Nat Neurosci. 2019;22(3):343-352. doi:10.1038/s41593-018-0326-7PubMedGoogle ScholarCrossref
Stahl  EA, Breen  G, Forstner  AJ,  et al; eQTLGen Consortium; BIOS Consortium; Bipolar Disorder Working Group of the Psychiatric Genomics Consortium.  Genome-wide association study identifies 30 loci associated with bipolar disorder.   Nat Genet. 2019;51(5):793-803. doi:10.1038/s41588-019-0397-8PubMedGoogle ScholarCrossref
Lee  JJ, Wedow  R, Okbay  A,  et al; 23andMe Research Team; COGENT (Cognitive Genomics Consortium); Social Science Genetic Association Consortium.  Gene discovery and polygenic prediction from a genome-wide association study of educational attainment in 1.1 million individuals.   Nat Genet. 2018;50(8):1112-1121. doi:10.1038/s41588-018-0147-3PubMedGoogle ScholarCrossref
Yengo  L, Sidorenko  J, Kemper  KE,  et al; GIANT Consortium.  Meta-analysis of genome-wide association studies for height and body mass index in ∼700 000 individuals of European ancestry.   Hum Mol Genet. 2018;27(20):3641-3649. doi:10.1093/hmg/ddy271PubMedGoogle ScholarCrossref
Dudbridge  F.  Power and predictive accuracy of polygenic risk scores.   PLoS Genet. 2013;9(3):e1003348. doi:10.1371/journal.pgen.1003348PubMedGoogle Scholar
Okbay  A, Baselmans  BML, De Neve  J-E,  et al; LifeLines Cohort Study.  Genetic variants associated with subjective well-being, depressive symptoms, and neuroticism identified through genome-wide analyses.   Nat Genet. 2016;48(6):624-633. doi:10.1038/ng.3552PubMedGoogle ScholarCrossref
Hammerschlag  AR, Stringer  S, de Leeuw  CA,  et al.  Genome-wide association analysis of insomnia complaints identifies risk genes and genetic overlap with psychiatric and metabolic traits.   Nat Genet. 2017;49(11):1584-1592. doi:10.1038/ng.3888PubMedGoogle ScholarCrossref
Vilhjálmsson  BJ, Yang  J, Finucane  HK,  et al; Schizophrenia Working Group of the Psychiatric Genomics Consortium, Discovery, Biology, and Risk of Inherited Variants in Breast Cancer (DRIVE) study.  Modeling linkage disequilibrium increases accuracy of polygenic risk scores.   Am J Hum Genet. 2015;97(4):576-592. doi:10.1016/j.ajhg.2015.09.001PubMedGoogle ScholarCrossref
Goodman  R.  The Strengths and Difficulties Questionnaire: a research note.   J Child Psychol Psychiatry. 1997;38(5):581-586. doi:10.1111/j.1469-7610.1997.tb01545.xPubMedGoogle ScholarCrossref
Larson  T, Anckarsäter  H, Gillberg  C,  et al.  The autism—tics, AD/HD and other comorbidities inventory (A-TAC): further validation of a telephone interview for epidemiological research.   BMC Psychiatry. 2010;10(1):1. doi:10.1186/1471-244X-10-1PubMedGoogle ScholarCrossref
Birmaher  B, Khetarpal  S, Brent  D,  et al.  The screen for child anxiety related emotional disorders (SCARED): scale construction and psychometric characteristics.   J Am Acad Child Adolesc Psychiatry. 1997;36(4):545-553. doi:10.1097/00004583-199704000-00018PubMedGoogle ScholarCrossref
Sharp  C, Goodyer  IM, Croudace  TJ.  The Short Mood and Feelings Questionnaire (SMFQ): a unidimensional item response theory and categorical data factor analysis of self-report ratings from a community sample of 7-through 11-year-old children.   J Abnorm Child Psychol. 2006;34(3):379-391. doi:10.1007/s10802-006-9027-xPubMedGoogle ScholarCrossref
Achenbach  TM.  Achenbach system of empirically based assessment (ASEBA).   The Encyclopedia of Clinical Psychology. 2014:1-8. doi:10.1002/9781118625392.wbecp150Google Scholar
Silva  RR, Alpert  M, Pouget  E,  et al.  A rating scale for disruptive behavior disorders, based on the DSM-IV item pool.   Psychiatr Q. 2005;76(4):327-339. doi:10.1007/s11126-005-4966-xPubMedGoogle ScholarCrossref
Conners  CK, Sitarenios  G, Parker  JD, Epstein  JN.  The revised Conners’ Parent Rating Scale (CPRS-R): factor structure, reliability, and criterion validity.   J Abnorm Child Psychol. 1998;26(4):257-268. doi:10.1023/A:1022602400621PubMedGoogle ScholarCrossref
Minică  CC, Dolan  CV, Kampert  MM, Boomsma  DI, Vink  JM.  Sandwich corrected standard errors in family-based genome-wide association studies.   Eur J Hum Genet. 2015;23(3):388-394. doi:10.1038/ejhg.2014.94PubMedGoogle ScholarCrossref
Viechtbauer  W.  Conducting meta-analyses in R with the metafor package.   J Stat Softw. 2010;36(3). doi:10.18637/jss.v036.i03Google Scholar
Nivard  MG, Gage  SH, Hottenga  JJ,  et al.  Genetic overlap between schizophrenia and developmental psychopathology: longitudinal and multivariate polygenic risk prediction of common psychiatric traits during development.   Schizophr Bull. 2017;43(6):1197-1207. doi:10.1093/schbul/sbx031PubMedGoogle ScholarCrossref
Nyholt  DR.  A simple correction for multiple testing for single-nucleotide polymorphisms in linkage disequilibrium with each other.   Am J Hum Genet. 2004;74(4):765-769. doi:10.1086/383251PubMedGoogle ScholarCrossref
Derringer  J. A simple correction for non-independent tests. Published March 21, 2018. Accessed March 2, 2020.
Calcagno  V, de Mazancourt  C.  glmulti: an R package for easy automated model selection with (generalized) linear models.   J Stat Softw. 2010;34(12):1-29. doi:10.18637/jss.v034.i12Google ScholarCrossref
Wagenmakers  E-J, Farrell  S.  AIC model selection using Akaike weights.   Psychon Bull Rev. 2004;11(1):192-196. doi:10.3758/BF03206482PubMedGoogle ScholarCrossref
Demontis  D, Walters  RK, Martin  J,  et al; ADHD Working Group of the Psychiatric Genomics Consortium (PGC); Early Lifecourse & Genetic Epidemiology (EAGLE) Consortium; 23andMe Research Team.  Discovery of the first genome-wide significant risk loci for attention deficit/hyperactivity disorder.   Nat Genet. 2019;51(1):63-75. doi:10.1038/s41588-018-0269-7PubMedGoogle ScholarCrossref
Baselmans  BML, Willems  YE, van Beijsterveldt  CEM,  et al.  Unraveling the genetic and environmental relationship between well-being and depressive symptoms throughout the lifespan.   Front Psychiatry. 2018;9(261):261. doi:10.3389/fpsyt.2018.00261PubMedGoogle ScholarCrossref
Mistry  S, Escott-Price  V, Florio  AD, Smith  DJ, Zammit  S.  Genetic risk for bipolar disorder and psychopathology from childhood to early adulthood.   J Affect Disord. 2019;246:633-639. doi:10.1016/j.jad.2018.12.091PubMedGoogle ScholarCrossref
Taylor  MJ, Martin  J, Lu  Y,  et al.  Association of genetic risk factors for psychiatric disorders and traits of these disorders in a Swedish population twin sample.   JAMA Psychiatry. 2019;76(3):280-289.PubMedGoogle ScholarCrossref
Singh  MK, DelBello  MP, Stanford  KE,  et al.  Psychopathology in children of bipolar parents.   J Affect Disord. 2007;102(1-3):131-136. doi:10.1016/j.jad.2007.01.004PubMedGoogle ScholarCrossref
Birmaher  B, Axelson  D, Monk  K,  et al.  Lifetime psychiatric disorders in school-aged offspring of parents with bipolar disorder: the Pittsburgh Bipolar Offspring study.   Arch Gen Psychiatry. 2009;66(3):287-296. doi:10.1001/archgenpsychiatry.2008.546PubMedGoogle ScholarCrossref
Selzam  S, Ritchie  SJ, Pingault  J-B, Reynolds  CA, O’Reilly  PF, Plomin  R.  Comparing within- and between-family polygenic score prediction.   Am J Hum Genet. 2019;105(2):351-363. doi:10.1016/j.ajhg.2019.06.006PubMedGoogle ScholarCrossref
Mostafavi  H, Harpak  A, Conley  D, Pritchard  JK, Przeworski  M.  Variable prediction accuracy of polygenic scores within an ancestry group.   bioRxiv. 2019. doi:10.1101/629949Google Scholar
Martin  J, Tilling  K, Hubbard  L,  et al.  Association of genetic risk for schizophrenia with nonparticipation over time in a population-based cohort study.   Am J Epidemiol. 2016;183(12):1149-1158. doi:10.1093/aje/kww009PubMedGoogle ScholarCrossref
Taylor  AE, Jones  HJ, Sallis  H,  et al.  Exploring the association of genetic factors with participation in the Avon Longitudinal Study of Parents and Children.   Int J Epidemiol. 2018;47(4):1207-1216. doi:10.1093/ije/dyy060PubMedGoogle ScholarCrossref
Allegrini  AG, Cheesman  R, Rimfeld  K,  et al.  The p factor: genetic analyses support a general dimension of psychopathology in childhood and adolescence.   J Child Psychol Psychiatry. 2020;61(1):30-39. doi:10.1111/jcpp.13113PubMedGoogle ScholarCrossref
Perkins  DO, Olde Loohuis  L, Barbee  J,  et al.  Polygenic risk score contribution to psychosis prediction in a target population of persons at clinical high risk.   Am J Psychiatry. 2020;177(2):155-163.PubMedGoogle ScholarCrossref
Chatterjee  N, Shi  J, García-Closas  M.  Developing and evaluating polygenic risk prediction models for stratified disease prevention.   Nat Rev Genet. 2016;17(7):392-406. doi:10.1038/nrg.2016.27PubMedGoogle ScholarCrossref
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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.


    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.