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The genetic etiology of childhood insomnia: Longitudinal gene-brain-behavior associations in the ABCD study

By Leanna M Hernandez, Minsoo Kim, Cristian Hernandez, Wesley Thompson, Chun Chieh Fan, Adriana Galván, Mirella Dapretto, Susan Y Bookheimer, Andrew Fuligni, Michael Gandal

Posted 05 Oct 2020
medRxiv DOI: 10.1101/2020.10.02.20204735

Childhood sleep problems are common and frequently comorbid with neurodevelopmental, psychiatric disorders. However, little is known about the genetic contributions to sleep-related traits in childhood, their potential relationship with brain development and psychiatric outcomes, or their association with adult sleep disturbance. Using data from the Adolescent Brain and Cognitive Development study, we performed a comprehensive characterization of the genetic and phenotypic relationships between childhood sleep disturbances (SDs; insomnia, arousal, breathing, somnolence, hyperhidrosis, sleep-wake transitions), global and regional measures of brain structure, and multiple dimensions of psychiatric symptomology in 9-10-year-old youth (discovery/replication N=4,428). Among the six SDs assessed, only insomnia showed significant SNP-based heritability (h2=0.15) and had replicable associations with smaller brain surface area (SA). Furthermore, insomnia showed significant positive phenotypic and genetic correlations with externalizing disorders (e.g., attention-deficit/hyperactivity disorder [ADHD]). Polygenic risk scores (PRS) calculated from genome-wide association studies (GWAS) of ADHD predicted insomnia and externalizing symptoms longitudinally, as well as decreased SA at baseline. In contrast, PRS trained using the largest adult insomnia GWAS did not predict childhood insomnia. Together, these findings demonstrate a distinct genetic architecture between childhood and adult SD, and indicate that childhood insomnia should be considered along the dimensional axis of ADHD and externalizing traits. These results highlight the importance of developmental context when interpreting gene-brain-behavior relationships and underscore the need for further large-scale genetic investigations of psychiatric phenotypes in pediatric populations.

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