Decoupling Sleep and Brain Size in Childhood: An Investigation of Genetic Covariation in the Adolescent Brain Cognitive Development Study
Year: 2022
Type: article
Abstract: Background Childhood sleep problems are common and among the most frequent and impairing comorbidities of childhood psychiatric disorders. However, little is known about the genetic architecture of childhood sleep and potential etiological links between sleep, brain morphology, and pediatric-onset psychiatric symptoms. Methods Using data from the Adolescent Brain and Cognitive Development Study (N Phenotype =4,428 for discovery/replication, N Genetics =4,728, age: 9-10), we assessed phenotypic relationships, heritability, and genetic correlation between childhood sleep disturbances (SDs: insomnia, arousal, breathing, somnolence, hyperhidrosis, sleep-wake transitions), brain size (surface area [SA], cortical thickness, volume), and dimensional psychopathology. Results SDs showed widespread positive associations with multiple domains of childhood psychopathology; however, only insomnia showed replicable associations with smaller brain SA. Among the SDs assessed, only insomnia showed significant SNP-based heritability ( h 2 SNP =0.15, p <0.05), and showed substantial genetic correlations with externalizing symptoms and attention-deficit hyperactivity disorder (ADHD; r G ’s>0.80, p ’s<0.05), suggesting significant pleiotropy across these complex childhood traits. We find no evidence of genetic correlation between childhood insomnia and brain size. Polygenic risk scores (PRS) calculated from genome-wide association studies (GWAS) of adult insomnia and adult brain size did not predict childhood insomnia; instead, PRS trained using ADHD GWAS predicted decreased SA at baseline, as well as insomnia and externalizing symptoms longitudinally. Conclusions These findings demonstrate a distinct genetic architecture underlying childhood insomnia and brain size and indicate that childhood insomnia should be considered along the dimensional axis of externalizing traits. Uncovering shared and unique genetic risk across childhood traits may inform our understanding of the developmental origins of comorbid psychiatric disorders.
Authors: Leanna M. Hernandez, Minsoo Kim, Cristian Hernandez, Wesley Thompson, Chun Chieh Fan, Adriana Galván, Mirella Dapretto, Susan Y. Bookheimer, Andrew Fuligni, Michael J. Gandal
Language: English
Topic: Sleep and related disorders
Subfield: Experimental and Cognitive Psychology
Field: Psychology
Domain: Social Sciences
Open Access status: gold
Estimated APC paid: $3,200
Funders: Simons Foundation Autism Research Initiative, National Institutes of Health, University of California, Los Angeles, National Institute of Mental Health, National Institute on Drug Abuse, National Institute of General Medical Sciences, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Awards: Isoform-level probabilistic transcriptome-wide association to undercover neurogenetic mechanisms underlying complex psychiatric traits, UCLA IDDRC, Functional genomic investigation of complement signaling in the human brain, UCLA-Caltech Medical Scientist Training Program, Training Grant in Neurobehavioral Genetics, Population-level and mechanistic dissection of 17q21 structural variant association with psychiatric traits, Gene-brain-environment interactions as determinants of typical and atypical developmental trajectories, 9/21 ABCD-USA CONSORTIUM: RESEARCH PROJECT SITE AT U MICHIGAN, 20/21 ABCD-USA CONSORTIUM: RESEARCH PROJECT SITE AT VCU, 3/21 ABCD-USA CONSORTIUM: RESEARCH PROJECT SITE AT U MINNESOTA, 4/21 ABCD-USA CONSORTIUM: RESEARCH PROJECT SITE AT FIU, 7/21 ABCD-USA CONSORTIUM: RESEARCH PROJECT SITE AT YALE, 17/21 ABCD-USA CONSORTIUM: RESEARCH PROJECT SITE AT UCLA, 15/21 ABCD-USA Consortium: Research Project Site at LIBR, 16/21 ABCD-USA CONSORTIUM: RESEARCH PROJECT SITE AT UNIVERSITY OF ROCHESTER, 8/21 ABCD-USA CONSORTIUM: RESEARCH PROJECT SITE AT CHLA, ABCD-USA Consortium: Coordinating Center, 6/21 ABCD-USA CONSORTIUM: RESEARCH PROJECT SITE AT OHSU, 10/21 ABCD-USA CONSORTIUM: RESEARCH PROJECT SITE AT SRI, 12/21 ABCD-USA CONSORTIUM: RESEARCH PROJECT SITE AT U PITTSBURGH, 19/21 ABCD-USA CONSORTIUM: RESEARCH PROJECT SITE AT UVM, 1/21 ABCD-USA CONSORTIUM: RESEARCH PROJECT SITE AT U UTAH, 11/21 ABCD-USA Consortium: Research Project Site at UWM, ABCD-USA Consortium: Data Analysis, Informatics and Resource Center, 21/21 ABCD-USA CONSORTIUM: RESEARCH PROJECT SITE AT WUSTL, 13/21 ABCD-USA CONSORTIUM: RESEARCH PROJECT SITE AT MUSC, 5/21 ABCD-USA Consortium: Research Project Site at UC San Diego, 18/21 ABCD-USA CONSORTIUM: RESEARCH PROJECT SITE AT THE UNIVERSITY OF FLORIDA, 2/21 ABCD-USA CONSORTIUM: RESEARCH PROJECT SITE AT UMB, 14/21 ABCD-USA Consortium: Research Project Site at CU Boulder
OpenAlex ID: W4206693556