Sleep-related traits and attention-deficit/hyperactivity disorder comorbidity: Shared genetic risk factors, molecular mechanisms, and causal effects
Autor: | Luciana Tovo-Rodrigues, Marina Xavier Carpena, Luis Augusto Rohde, Thais Martins-Silva, Julia P. Genro, Carolina Bonilla, Alicia Matijasevich, Mara H. Hutz |
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Rok vydání: | 2021 |
Předmět: |
Sleep Wake Disorders
Comorbidity 03 medical and health sciences 0302 clinical medicine Risk Factors mental disorders Mendelian randomization Insomnia medicine Humans Attention deficit hyperactivity disorder Circadian rhythm Association (psychology) Biological Psychiatry Genetic association business.industry Causal effect Chronotype medicine.disease Summary statistics Sleep in non-human animals 030227 psychiatry Psychiatry and Mental health Phenotype Attention Deficit Disorder with Hyperactivity medicine.symptom Sleep business Genome-Wide Association Study Clinical psychology |
Zdroj: | The World Journal of Biological Psychiatry. 22:778-791 |
ISSN: | 1814-1412 1562-2975 |
DOI: | 10.1080/15622975.2021.1907719 |
Popis: | Study ObjectivesTo evaluate the level of shared genetic components between attention-deficit/hyperactivity disorder (ADHD) and sleep phenotype, common pathways between them and a possible causal relationship between traits.MethodsWe used summary statistics of the largest genome-wide association studies available for ADHD and sleep-related phenotypes including insomnia, napping, daytime dozing, snoring, ease getting up, daytime sleepiness, sleep duration and chronotype. We estimated the genomic correlation between ADHD and sleep-related traits using cross-trait LD-score regression and investigated potential common mechanisms using gene-based cross-trait metanalyses and functional enrichment analyses. The causal effect between the sleep related traits and ADHD was estimated with two sample Mendelian randomization (TSMR), using the Inverse Variance Weighted method as the main estimator.ResultsPositive genomic correlation between insomnia, daytime napping, daytime dozing, snoring, daytime sleepiness, short and long sleep duration, and ADHD were observed. Insomnia, sleep duration, daytime sleepiness, and snoring shared genes with ADHD, which were involved in neurobiological functions and regulatory signaling pathways. The TSMR approach supported a causal effect of insomnia, daytime napping, and short sleep duration on ADHD, and of ADHD on long sleep duration and chronotype.ConclusionOur findings suggest that the comorbidity between sleep phenotypes and ADHD may be mediated by common genetic factors with an important role on neuronal signaling pathways. In addition, it may also exist a causal effect of sleep disturbances and short sleep duration on ADHD, reinforcing the role of these sleep phenotypes as predictors or early markers of ADHD.Statement of SignificanceOur findings suggest that the comorbidity between sleep phenotypes and ADHD may be linked to common genetic factors with an important role on neuronal signaling pathways. They also show that a causal effect of sleep disturbances and short sleep duration on ADHD may exist, reinforcing the role of these sleep phenotypes as ADHD early markers, being able to predict the disorder. This study adds important information about the relationship between sleep, circadian rhythm, and ADHD since it raises new questions about the complexity of the phenomenon involving them and may also provide new treatment insights in this research field. |
Databáze: | OpenAIRE |
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