title: Heritability and Genome-Wide Association Analyses of Sleep Duration in Children: The EAGLE Consortium.
abstract: Low or excessive sleep duration has been associated with multiple outcomes, but the biology behind these associations remains elusive. Specifically, genetic studies in children are scarce. In this study, we aimed to: (1) estimate the proportion of genetic variance of sleep duration in children attributed to common single nucleotide polymorphisms (SNPs), (2) identify novel SNPs associated with sleep duration in children, and (3) investigate the genetic overlap of sleep duration in children and related metabolic and psychiatric traits.
  
  
  
  We performed a population-based molecular genetic study, using data form the EArly Genetics and Life course Epidemiology (EAGLE) Consortium. 10,554 children of European ancestry were included in the discovery, and 1,250 children in the replication phase.
  
  
  
  We found evidence of significant but modest SNP heritability of sleep duration in children (SNPh20.14, 95% CI [0.05, 0.23]) using the LD score regression method. A novel region at chromosome 11q13.4 (top SNP: rs74506765, P = 2.27e-08) was associated with sleep duration in children, but this was not replicated in independent studies. Nominally significant genetic overlap was only found (rG= 0.23, P = 0.05) between sleep duration in children and type 2 diabetes in adults, supporting the hypothesis of a common pathogenic mechanism.
  
  
  
  The significant SNP heritability of sleep duration in children and the suggestive genetic overlap with type 2 diabetes support the search for genetic mechanisms linking sleep duration in children to multiple outcomes in health and disease.
authors: Agency for Healthcare Quality and Evaluation of Catalonia (AQuAS), Roc Boronat, Barcelona, Spain.|Spanish Consortium for Research on Epidemiology and Public Health (CIBERESP), Madrid, Spain.|ISGlobal, Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain.
authors: Marcella
authors: M
authors: Marinelli
authors: School of Pedagogical and Educational Sciences, Erasmus University Rotterdam, The Netherlands.|Generation R Study Group, Erasmus Medical Center, Rotterdam, The Netherlands.
authors: Irene
authors: I
authors: Pappa
authors: Spanish Consortium for Research on Epidemiology and Public Health (CIBERESP), Madrid, Spain.|ISGlobal, Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain.|Centre for Genomic Regulation (CRG), the Barcelona Institute of Science and Technology, Barcelona, Spain.|Universitat Pompeu Fabra (UPF), Barcelona, Spain.
authors: Mariona
authors: M
authors: Bustamante
authors: School of Social and Community Medicine, University of Bristol, Bristol, UK.|MRC/University of Bristol Integrative Epidemiology Unit, University of Bristol, Bristol, UK.
authors: Carolina
authors: C
authors: Bonilla
authors: Institute of behavioural sciences, University of Helsinki, Helsinki, Finland.
authors: Anna
authors: A
authors: Suarez
authors: Institute of Epidemiology I, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany.|Ludwig-Maximilians-University of Munich, Dr. von Hauner Children's Hospital, Division of Metabolic Diseases and Nutritional Medicine, Munich, Germany.
authors: Carla M
authors: CM
authors: Tiesler
authors: Spanish Consortium for Research on Epidemiology and Public Health (CIBERESP), Madrid, Spain.|ISGlobal, Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain.|Universitat Pompeu Fabra (UPF), Barcelona, Spain.
authors: Natalia
authors: N
authors: Vilor-Tejedor
authors: Department of Public Health, Academic Medical Center (AMC), University of Amsterdam, The Netherlands.|Department of Obstetrics and Gynaecology, Academic Medical Centre, University of Amsterdam, The Netherlands.
authors: Mohammad Hadi
authors: MH
authors: Zafarmand
authors: Spanish Consortium for Research on Epidemiology and Public Health (CIBERESP), Madrid, Spain.|ISGlobal, Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain.|Universitat Pompeu Fabra (UPF), Barcelona, Spain.
authors: Mar
authors: M
authors: Alvarez-Pedrerol
authors: Children's Hospital, University of Helsinki, and Helsinki University Hospital, Helsinki, Finland.
authors: Sture
authors: S
authors: Andersson
authors: Centre for Child and Family Studies, Leiden University, Leiden, The Netherlands.
authors: Marian J
authors: MJ
authors: Bakermans-Kranenburg
authors: Spanish Consortium for Research on Epidemiology and Public Health (CIBERESP), Madrid, Spain.|Centre for Genomic Regulation (CRG), the Barcelona Institute of Science and Technology, Barcelona, Spain.|Universitat Pompeu Fabra (UPF), Barcelona, Spain.|Institut Hospital del Mar d'Investigacions Mediques (IMIM), 08003 Barcelona, Spain.
authors: Xavier
authors: X
authors: Estivill
authors: School of Social and Community Medicine, University of Bristol, Bristol, UK.|MRC/University of Bristol Integrative Epidemiology Unit, University of Bristol, Bristol, UK.|University of Queensland Diamantina Institute, Translational Research Institute, Brisbane, Queensland, Australia.
authors: David M
authors: DM
authors: Evans
authors: Institute of Epidemiology I, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany.
authors: Claudia
authors: C
authors: Flexeder
authors: Spanish Consortium for Research on Epidemiology and Public Health (CIBERESP), Madrid, Spain.|Universitat Pompeu Fabra (UPF), Barcelona, Spain.
authors: Joan
authors: J
authors: Forns
authors: Spanish Consortium for Research on Epidemiology and Public Health (CIBERESP), Madrid, Spain.|ISGlobal, Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain.|Universitat Pompeu Fabra (UPF), Barcelona, Spain.
authors: Juan R
authors: JR
authors: Gonzalez
authors: Spanish Consortium for Research on Epidemiology and Public Health (CIBERESP), Madrid, Spain.|ISGlobal, Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain.|Universitat Pompeu Fabra (UPF), Barcelona, Spain.|Department of Child and Adolescent Psychiatry/Psychology, Erasmus Medical Center-Sophia Children's Hospital, Rotterdam, the Netherlands.
authors: Monica
authors: M
authors: Guxens
authors: Institute for Risk Assessment Sciences, Utrecht University, the Netherlands.
authors: Anke
authors: A
authors: Huss
authors: School of Pedagogical and Educational Sciences, Erasmus University Rotterdam, The Netherlands.|Generation R Study Group, Erasmus Medical Center, Rotterdam, The Netherlands.|Centre for Child and Family Studies, Leiden University, Leiden, The Netherlands.
authors: Marinus H
authors: MH
authors: van IJzendoorn
authors: Generation R Study Group, Erasmus Medical Center, Rotterdam, The Netherlands.|Department of Epidemiology, Erasmus Medical Center-Sophia Children's Hospital, Rotterdam, The Netherlands.|Department of Pediatrics, Erasmus Medical Center- Sophia Children's Hospital, Rotterdam, The Netherlands.
authors: Vincent W V
authors: VW
authors: Jaddoe
authors: Spanish Consortium for Research on Epidemiology and Public Health (CIBERESP), Madrid, Spain.|ISGlobal, Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain.|Universitat Pompeu Fabra (UPF), Barcelona, Spain.
authors: Jordi
authors: J
authors: Julvez
authors: Institute of behavioural sciences, University of Helsinki, Helsinki, Finland.|Helsinki Collegium for Advanced Studies, Helsinki, Finland.|Folkhälsan Research Centre, Finland.
authors: Jari
authors: J
authors: Lahti
authors: Spanish Consortium for Research on Epidemiology and Public Health (CIBERESP), Madrid, Spain.|ISGlobal, Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain.|Universitat Pompeu Fabra (UPF), Barcelona, Spain.
authors: Mónica
authors: M
authors: López-Vicente
authors: Spanish Consortium for Research on Epidemiology and Public Health (CIBERESP), Madrid, Spain.|Epidemiology and Environmental Health Joint Research Unit, FISABIO, Universitat Jaume I, Universitat de València, Spain.
authors: Maria-Jose
authors: MJ
authors: Lopez-Espinosa
authors: Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.|Institute of Epidemiology II, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
authors: Judith
authors: J
authors: Manz
authors: Centre for Child and Family Studies, Leiden University, Leiden, The Netherlands.
authors: Viara R
authors: VR
authors: Mileva-Seitz
authors: Public Health Genomics Unit and Institute for Molecular Medicine FIMM, University of Helsinki, Finland.|National Institute for Health and Welfare, Helsinki, Finland.
authors: Markus
authors: M
authors: Perola
authors: Institute of behavioural sciences, University of Helsinki, Helsinki, Finland.
authors: Anu-Katriina
authors: AK
authors: Pesonen
authors: Generation R Study Group, Erasmus Medical Center, Rotterdam, The Netherlands.|Department of Epidemiology, Erasmus Medical Center-Sophia Children's Hospital, Rotterdam, The Netherlands.|Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands.
authors: Fernando
authors: F
authors: Rivadeneira
authors: Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.|Genomics and Biomarkers Unit, National Institute for Health and Welfare, Helsinki, Finland.
authors: Perttu P
authors: PP
authors: Salo
authors: Department of Clinical Epidemiology Biostatistics and Bioinformatics, Academic Medical Center (AMC), University of Amsterdam, The Netherlands.
authors: Shayan
authors: S
authors: Shahand
authors: Institute of Epidemiology I, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany.
authors: Holger
authors: H
authors: Schulz
authors: Institute of Epidemiology I, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany.
authors: Marie
authors: M
authors: Standl
authors: Institute of Epidemiology I, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany.|Ludwig-Maximilians-University of Munich, Dr. von Hauner Children's Hospital, Division of Metabolic Diseases and Nutritional Medicine, Munich, Germany.
authors: Elisabeth
authors: E
authors: Thiering
authors: School of Social and Community Medicine, University of Bristol, Bristol, UK.|MRC/University of Bristol Integrative Epidemiology Unit, University of Bristol, Bristol, UK.
authors: Nicholas J
authors: NJ
authors: Timpson
authors: Ib-salut- Area de Salut de Menorca, Spain.
authors: Maties
authors: M
authors: Torrent
authors: Department of Epidemiology, Erasmus Medical Center-Sophia Children's Hospital, Rotterdam, The Netherlands.|Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands.|Netherlands Genomics Initiative (NGI)-sponsored Netherlands Consortium for Healthy Aging (NCHA), Leiden, The Netherlands.
authors: André G
authors: AG
authors: Uitterlinden
authors: School of Social and Community Medicine, University of Bristol, Bristol, UK.|MRC/University of Bristol Integrative Epidemiology Unit, University of Bristol, Bristol, UK.
authors: George Davey
authors: GD
authors: Smith
authors: Spanish Consortium for Research on Epidemiology and Public Health (CIBERESP), Madrid, Spain.|Epidemiology and Environmental Health Joint Research Unit, FISABIO, Universitat Jaume I, Universitat de València, Spain.
authors: Marisa
authors: M
authors: Estarlich
authors: Institute of Epidemiology I, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany.
authors: Joachim
authors: J
authors: Heinrich
authors: Institute of behavioural sciences, University of Helsinki, Helsinki, Finland.
authors: Katri
authors: K
authors: Räikkönen
authors: Department of Public Health, Academic Medical Center (AMC), University of Amsterdam, The Netherlands.
authors: Tanja G M
authors: TG
authors: Vrijkotte
authors: Department of Child and Adolescent Psychiatry/Psychology, Erasmus Medical Center-Sophia Children's Hospital, Rotterdam, the Netherlands.|Department of Epidemiology, Erasmus Medical Center-Sophia Children's Hospital, Rotterdam, The Netherlands.|Department of Psychiatry, Erasmus Medical Center, Rotterdam, The Netherlands.
authors: Henning
authors: H
authors: Tiemeier
authors: Spanish Consortium for Research on Epidemiology and Public Health (CIBERESP), Madrid, Spain.|ISGlobal, Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain.|Universitat Pompeu Fabra (UPF), Barcelona, Spain.|Institut Hospital del Mar d'Investigacions Mediques (IMIM), 08003 Barcelona, Spain.
authors: Jordi
authors: J
authors: Sunyer
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology / Q000235:genetics; D005260:Female; D055106:Genome-Wide Association Study / Q000379:methods*; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D019655:Quantitative Trait, Heritable; D012890:Sleep / Q000235:genetics*; D013997:Time Factors; D044465:White People / Q000235:genetics
keywords: SNP heritability; childhood sleep duration; genome-wide association study (GWAS); meta-analysis; pathway analysis