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

Abstract

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 42998 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.

This meta-analysis combines data from 7 previous cohorts in the UK, Netherlands, Sweden, Norway, and Finland to investigate whether genetic risk for adult mood disorders and associated traits are associated with childhood disorders.

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 42998 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 (beta 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 (beta, -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 (Delta beta, 0.0561 [Delta 95% CI, 0.0318-0.0804]; Delta SE, 0.0124) and social problems (Delta beta, 0.0528 [Delta 95% CI, 0.0282-0.0775]; Delta SE, 0.0126), and between BMI PGS and ADHD and social problems (Delta beta, -0.0001 [Delta 95% CI, -0.0102 to 0.0100]; Delta SE, 0.0052), compared with internalizing problems (Delta beta, -0.0310 [Delta 95% CI, -0.0456 to -0.0164]; Delta SE, 0.0074). Furthermore, the association between educational attainment PGS and ADHD increased with age (Delta beta, -0.0032 [Delta 95% CI, -0.0048 to -0.0017]; Delta SE, 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.