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Mol Psychiatry. 2015 Oct;20(10):1232-9. doi: 10.1038/mp.2014.133. Epub 2014 Dec 2.

Novel loci associated with usual sleep duration: the CHARGE Consortium Genome-Wide Association Study.

Author information

1
VA Boston Healthcare System, Boston, MA, USA.
2
Division of Sleep and Circadian Disorders, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.
3
Department of Medicine, Boston University School of Medicine, Boston, MA, USA.
4
The NHLBI's Framingham Heart Study, Framingham, MA, USA.
5
Department of Epidemiology, Erasmus MC, Rotterdam, The Netherlands.
6
Epidemiological and Social Psychiatric Research Institute, Department of Psychiatry, Erasmus MC, Rotterdam, The Netherlands.
7
Department of Neurology, University of Washington, Seattle, WA, USA.
8
UW Medicine Sleep Center, University of Washington, Seattle, WA, USA.
9
Icelandic Heart Association, Kópavogur, Iceland.
10
The University of Queensland, Queensland Brain Institute, St Lucia, QLD, Australia.
11
Queensland Institute of Medical Research, Brisbane, QLD, Australia.
12
Department of Nutrition, Harvard School of Public Health, Boston, MA, USA.
13
Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
14
Center for Sleep Sciences and Medicine, Stanford University, Palo Alto, CA, USA.
15
Geriatric Unit, Azienda Sanitaria Firenze (ASF), Florence, Italy.
16
Department of Twin Research and Genetic Epidemiology, King's College London, London, UK.
17
California Pacific Medical Center Research Institute, San Francisco, CA, USA.
18
Department of Psychiatry and Psychotherapy, HELIOS-Hospital Stralsund, University Medicine Greifswald, Greifswald, Germany.
19
Institute of Behavioural Sciences, University of Helsinki, Helsinki, Finland.
20
Folkhalsan Research Centre, Helsinki, Finland.
21
Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA.
22
Department of Clinical Chemistry, Fimlab Laboratories and School of Medicine, University of Tampere, Tampere, Finland.
23
Department of Statistics, University of Auckland, Auckland, New Zealand.
24
Department of Medicine, University of Washington, Seattle, WA, USA.
25
Cardiovascular Health Research Unit, University of Washington, Seattle, WA, USA.
26
Department of Kinesiology, Laval University, Quebec, Canada.
27
Institute of Nutrition and Functional Foods, Laval University, Quebec, Canada.
28
Department of Epidemiology and Health Services, University of Washington, Seattle, WA, USA.
29
Group Health Research Institute, Group Health Cooperative, Seattle, WA, USA.
30
Department of Internal Medicine, University of California Davis, Sacramento, CA, USA.
31
Department of Biological Psychology, Netherlands Twin Register, VU University, Amsterdam, The Netherlands.
32
Precision Medicine, Cambridge, MA, USA.
33
Division of Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, NC, USA.
34
Texas Biomedical Research Institute, San Antonio, TX, USA.
35
Department of Prosthodontics, Gerodontology and Dental Materials, Center of Oral Health, University Medicine Greifswald, Greifswald, Germany.
36
Pennington Biomedical Research Center, Baton Rouge, LA, USA.
37
Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA.
38
Department of General Practice and Primary Health Care, University of Helsinki, Helsinki, Finland.
39
Helsinki University Central Hospital, Helsinki, Finland.
40
National Institute for Health and Welfare, Helsinki, Finland.
41
Vasa Central Hospital, Vasa, Finland.
42
Department of Internal Medicine B-Cardiology, Pulmonary Medicine, Infectious Diseases and Intensive Care Medicine, University Medicine Greifswald, Greifswald, Germany.
43
Translational Gerontology Branch, National Institute on Aging, Baltimore, MD, USA.
44
Department of Medicine, University of Mississippi Medical Center, Jackson, MS, USA.
45
Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
46
Center for Human Genetics Research, Vanderbilt University Medical Center, Nashville, TN, USA.
47
Laboratory of Epidemiology, Demography, and Biometry, National Institute on Aging, Bethesda, MD, USA.
48
Department of Psychiatry, Washington University School of Medicine, St Louis, MO, USA.
49
Laboratory of Neurogenetics, National Institute on Aging, Bethesda, MD, USA.
50
Program in Molecular and Genetic Epidemiology, Harvard School of Public Health, Boston, MA, USA.
51
NHLBI Cardiovascular Epidemiology and Human Genomics Branch, The Framingham Heart Study, Framingham, MA, USA.
52
Department of Clinical Physiology, Tampere University Hospital and School of Medicine University of Tampere, Tampere, Finland.
53
Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA.
54
Department of Health Studies, University of Chicago, Chicago, IL, USA.
55
Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands.
56
Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.
57
Program in Medical and Population Genetics and Genetic Analysis Platform, The Broad Institute of MIT and Harvard, Cambridge, MA, USA.
58
Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge, UK.
59
Division of Genetics and Cell Biology, San Raffaele Research Institute, Milano, Italy.
60
Universita' degli Studi di Trieste, Trieste, Italy.
61
Istituto di Ricerca Genetica e Biomedica (IRGB), Consiglio Nazionale delle Ricerche, c/o Cittadella Universitaria di Monserrato, Monserrato, Cagliari, Italy.
62
Dipartimento di Scienze Biomediche, Universita' di Sassari, Sassari, Italy.
63
Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, and Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku, Finland.
64
Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute and Department of Pediatrics, Harbor-UCLA Medical Center, Torrance, CA, USA.
65
University of Iceland, Reykjavik, Iceland.
66
Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Greifswald, Germany.
67
Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany.
68
Netherlands Genomics Initiative-sponsored Netherlands Consortium for Healthy Aging, Leiden, The Netherlands.
69
Department of Food Science and Nutrition, Laval University, Quebec, Canada.
70
Department of Population Health Sciences, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA.
71
Department of Medicine, Turku University Hospital and University of Turku, Turku, Finland.
72
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
73
Department of Child and Adolescent Psychiatry, Erasmus MC, Rotterdam, The Netherlands.

Abstract

Usual sleep duration is a heritable trait correlated with psychiatric morbidity, cardiometabolic disease and mortality, although little is known about the genetic variants influencing this trait. A genome-wide association study (GWAS) of usual sleep duration was conducted using 18 population-based cohorts totaling 47 180 individuals of European ancestry. Genome-wide significant association was identified at two loci. The strongest is located on chromosome 2, in an intergenic region 35- to 80-kb upstream from the thyroid-specific transcription factor PAX8 (lowest P=1.1 × 10(-9)). This finding was replicated in an African-American sample of 4771 individuals (lowest P=9.3 × 10(-4)). The strongest combined association was at rs1823125 (P=1.5 × 10(-10), minor allele frequency 0.26 in the discovery sample, 0.12 in the replication sample), with each copy of the minor allele associated with a sleep duration 3.1 min longer per night. The alleles associated with longer sleep duration were associated in previous GWAS with a more favorable metabolic profile and a lower risk of attention deficit hyperactivity disorder. Understanding the mechanisms underlying these associations may help elucidate biological mechanisms influencing sleep duration and its association with psychiatric, metabolic and cardiovascular disease.

PMID:
25469926
PMCID:
PMC4430294
DOI:
10.1038/mp.2014.133
[Indexed for MEDLINE]
Free PMC Article

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