childhood and adolescent internalising symptoms

Introduction

  • Study Title: Genome-wide Association Meta-analysis of Childhood and Adolescent Internalizing Symptoms

  • Authors: Eshim S. Jami, Anke R. Hammerschlag, Hill F. Ip, Andrea G. Allegrini, et al.

  • Objective: Investigate genetic architecture of internalizing symptoms in childhood/adolescence.

Methodology

  • Sample Size: 22 cohorts, repeated assessments of internalizing symptoms involving 64,561 children/adolescents aged 3-18.

  • Assessment Types: Included multiple/univariate GWASs (Genome-Wide Association Studies), aggregated in meta-analyses.

  • Main Analyses: Assessed heritability, genetic correlations by rater, age, and instrument.

Findings

  • General Results:

    • Meta-analysis of INToverall (overall internalizing symptoms).

    • No genome-wide significant hits found.

    • SNP heritability: 1.66% (95% CI: 0.84%-2.48%).

  • Heritability Analysis:

    • Self-reported internalizing symptoms had highest heritability: 5.63% (95% CI: 3.08%-8.18%).

    • Stability in additive genetic effects across ages.

    • Genetic correlations with adult anxiety and depression (|rg| > 0.70).

  • Other Factors:

    • Notable genetic correlations with insomnia, ADHD, autism, and childhood aggression (|rg| 0.42-0.60).

    • No significant correlations with schizophrenia, bipolar disorder, OCD.

Conclusion

  • Internalizing symptoms in childhood signal genetic vulnerabilities shared with adult psychiatric disorders.

  • Addressing phenotypic heterogeneity in childhood samples crucial for advancing GWAS success.

  • Key concepts include depression, anxiety, repeated measures, genetic epidemiology, and molecular genetics.

Key Statistics

  • Sample Overlap: Effective sample size of 132,260.

  • Psychological impact: Internalizing disorders significantly burden global health.

  • Epidemiology: Childhood depression prevalence at 2-3%, anxiety at 6-7%.

Genetic Components

  • Estimates indicate that genetic factors explain 40% to 50% variance in internalizing symptoms.

  • Limited research on molecular genetic architecture for early life internalizing symptoms until now; earlier studies yielded no genome-wide significant hits.

Methodological Innovations

  • In-depth meta-analyses employed N-weighed methods to adjust for repeated measurements

  • Used MAGMA for gene-based analysis and assessed tissue specificity.

  • Genetic correlations derived using public datasets to explore broader connections with traits like neuroticism.

Limitations

  • Current findings apply primarily to individuals of European ancestry.

  • Low SNP heritability raises questions about the detectability of strong associations.

  • Suggests future studies to consider sex-differentiated analyses and multi-ancestry cohorts for broader applicability.

Future Directions

  • Future GWAS must focus on reducing rater heterogeneity in childhood studies.

  • Enhancing sample sizes and methodological robustness critical for discovering specific genomic loci.

  • Integrative approaches considering common conditions like depression and anxiety could enhance understanding of genetic contributions to internalizing symptoms.