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Sleep. 2016 Oct 1;39(10):1859-1869.

Heritability and Genome-Wide Association Analyses of Sleep Duration in Children: The EAGLE Consortium.

Author information

1
Agency for Healthcare Quality and Evaluation of Catalonia (AQuAS), Roc Boronat, Barcelona, Spain.
2
Spanish Consortium for Research on Epidemiology and Public Health (CIBERESP), Madrid, Spain.
3
ISGlobal, Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain.
4
School of Pedagogical and Educational Sciences, Erasmus University Rotterdam, The Netherlands.
5
Generation R Study Group, Erasmus Medical Center, Rotterdam, The Netherlands.
6
Centre for Genomic Regulation (CRG), the Barcelona Institute of Science and Technology, Barcelona, Spain.
7
Universitat Pompeu Fabra (UPF), Barcelona, Spain.
8
School of Social and Community Medicine, University of Bristol, Bristol, UK.
9
MRC/University of Bristol Integrative Epidemiology Unit, University of Bristol, Bristol, UK.
10
Institute of behavioural sciences, University of Helsinki, Helsinki, Finland.
11
Institute of Epidemiology I, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany.
12
Ludwig-Maximilians-University of Munich, Dr. von Hauner Children's Hospital, Division of Metabolic Diseases and Nutritional Medicine, Munich, Germany.
13
Department of Public Health, Academic Medical Center (AMC), University of Amsterdam, The Netherlands.
14
Department of Obstetrics and Gynaecology, Academic Medical Centre, University of Amsterdam, The Netherlands.
15
Children's Hospital, University of Helsinki, and Helsinki University Hospital, Helsinki, Finland.
16
Centre for Child and Family Studies, Leiden University, Leiden, The Netherlands.
17
Institut Hospital del Mar d'Investigacions Mediques (IMIM), 08003 Barcelona, Spain.
18
University of Queensland Diamantina Institute, Translational Research Institute, Brisbane, Queensland, Australia.
19
Department of Child and Adolescent Psychiatry/Psychology, Erasmus Medical Center-Sophia Children's Hospital, Rotterdam, the Netherlands.
20
Institute for Risk Assessment Sciences, Utrecht University, the Netherlands.
21
Department of Epidemiology, Erasmus Medical Center-Sophia Children's Hospital, Rotterdam, The Netherlands.
22
Department of Pediatrics, Erasmus Medical Center- Sophia Children's Hospital, Rotterdam, The Netherlands.
23
Helsinki Collegium for Advanced Studies, Helsinki, Finland.
24
Folkhälsan Research Centre, Finland.
25
Epidemiology and Environmental Health Joint Research Unit, FISABIO, Universitat Jaume I, Universitat de València, Spain.
26
Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
27
Institute of Epidemiology II, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
28
Public Health Genomics Unit and Institute for Molecular Medicine FIMM, University of Helsinki, Finland.
29
National Institute for Health and Welfare, Helsinki, Finland.
30
Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands.
31
Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.
32
Genomics and Biomarkers Unit, National Institute for Health and Welfare, Helsinki, Finland.
33
Department of Clinical Epidemiology Biostatistics and Bioinformatics, Academic Medical Center (AMC), University of Amsterdam, The Netherlands.
34
Ib-salut- Area de Salut de Menorca, Spain.
35
Netherlands Genomics Initiative (NGI)-sponsored Netherlands Consortium for Healthy Aging (NCHA), Leiden, The Netherlands.
36
Department of Psychiatry, Erasmus Medical Center, Rotterdam, The Netherlands.

Abstract

STUDY OBJECTIVES:

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.

METHODS:

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.

RESULTS:

We found evidence of significant but modest SNP heritability of sleep duration in children (SNP h2 0.14, 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.

CONCLUSIONS:

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.

KEYWORDS:

SNP heritability; childhood sleep duration; genome-wide association study (GWAS); meta-analysis; pathway analysis

PMID:
27568811
PMCID:
PMC5020368
DOI:
10.5665/sleep.6170
[Indexed for MEDLINE]
Free PMC Article

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