Marina Xavier Carpena1, Carolina Bonilla2,3, Alicia Matijasevich1,2, Thais Martins-Silva1, Julia P Genro4, Mara Helena Hutz5, Luis Augusto Rohde6, Luciana Tovo-Rodrigues1. 1. Post-Graduate Program in Epidemiology, Federal University of Pelotas, Pelotas, Brazil. 2. Departamento de Medicina Preventiva, Faculdade de Medicina FMUSP, Universidade de São Paulo, SP, Brasil. 3. Population Health Sciences, University of Bristol, Bristol, UK. 4. Graduate Program in Biosciences, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, Brazil. 5. Department of Genetics, Federal University of Rio Grande do Sul, Porto Alegre, Brazil. 6. Federal University of Rio Grande do Sul, Department of Psychiatry, Child & Adolescent Psychiatry Unit, Hospital de Clinicas de Porto Alegre, Porto Alegre, Brazil.
Abstract
OBJECTIVES: To evaluate the shared genetic components, common pathways and causal relationship between ADHD and sleep-related phenotypes. METHODS: We used the largest genome-wide association summary statistics available for attention-deficit/hyperactivity disorder (ADHD) and various sleep-related phenotypes (insomnia, napping, daytime dozing, snoring, ease getting up, daytime sleepiness, sleep duration and chronotype). We estimated the genomic correlation using cross-trait linkage disequilibrium score regression (LDSR) and investigated the potential common mechanisms using gene-based cross-trait metanalyses and functional enrichment analyses. The causal effect was estimated using two-sample Mendelian randomisation (TSMR), using the inverse variance weighted method as the main estimator. RESULTS: A positive genomic correlation between insomnia, daytime napping, daytime dozing, snoring, daytime sleepiness, short and long sleep duration, and ADHD was observed. Insomnia, daytime sleepiness, and snoring shared genes with ADHD, that are involved in neurobiological functions and regulatory signalling pathways. The TSMR supported a causal effect of insomnia, daytime napping, and short sleep duration on ADHD, and of ADHD on long sleep duration and chronotype. CONCLUSION: Comorbidity between sleep phenotypes and ADHD may be mediated by common genetic factors that play an important role in neuronal signalling pathways. A causal effect of sleep disturbances and short sleep duration on ADHD reinforced their role as predictors of ADHD.
OBJECTIVES: To evaluate the shared genetic components, common pathways and causal relationship between ADHD and sleep-related phenotypes. METHODS: We used the largest genome-wide association summary statistics available for attention-deficit/hyperactivity disorder (ADHD) and various sleep-related phenotypes (insomnia, napping, daytime dozing, snoring, ease getting up, daytime sleepiness, sleep duration and chronotype). We estimated the genomic correlation using cross-trait linkage disequilibrium score regression (LDSR) and investigated the potential common mechanisms using gene-based cross-trait metanalyses and functional enrichment analyses. The causal effect was estimated using two-sample Mendelian randomisation (TSMR), using the inverse variance weighted method as the main estimator. RESULTS: A positive genomic correlation between insomnia, daytime napping, daytime dozing, snoring, daytime sleepiness, short and long sleep duration, and ADHD was observed. Insomnia, daytime sleepiness, and snoring shared genes with ADHD, that are involved in neurobiological functions and regulatory signalling pathways. The TSMR supported a causal effect of insomnia, daytime napping, and short sleep duration on ADHD, and of ADHD on long sleep duration and chronotype. CONCLUSION: Comorbidity between sleep phenotypes and ADHD may be mediated by common genetic factors that play an important role in neuronal signalling pathways. A causal effect of sleep disturbances and short sleep duration on ADHD reinforced their role as predictors of ADHD.
Authors: Miguel Garcia-Argibay; Ebba du Rietz; Yi Lu; Joanna Martin; Elis Haan; Kelli Lehto; Sarah E Bergen; Paul Lichtenstein; Henrik Larsson; Isabell Brikell Journal: Transl Psychiatry Date: 2022-04-11 Impact factor: 7.989