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Nat Genet. 2017 Feb;49(2):274-281. doi: 10.1038/ng.3749. Epub 2016 Dec 19.

Genome-wide association analyses of sleep disturbance traits identify new loci and highlight shared genetics with neuropsychiatric and metabolic traits.

Author information

1
Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts, USA.
2
Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
3
Broad Institute, Cambridge, Massachusetts, USA.
4
Department of Epidemiology and Biostatistics, School of Medicine, Case Western Reserve University, Cleveland, Ohio, USA.
5
Division of Cardiovascular Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.
6
George Institute for Global Health, University of Oxford, Oxford Martin School, Oxford, UK.
7
Division of Endocrinology, Diabetes and Gastroenterology, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.
8
MRC Integrative Epidemiology Unit at the University of Bristol, Bristol, UK.
9
School of Social and Community Medicine, University of Bristol, Bristol, UK.
10
Division of Population Health, Health Services Research and Primary Care, School of Health Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK.
11
Engineering and Applied Science, Aston University, Birmingham, UK.
12
Media Laboratory, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
13
Sleep and Circadian Neuroscience Institute, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK.
14
Division of Sleep and Circadian Disorders, Brigham and Women's Hospital and Division of Sleep Medicine, Harvard Medical School, Boston, Massachusetts, USA.
15
Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
16
Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
17
Department of Medicine, Brigham and Women's Hospital and Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.
18
Manchester Diabetes Centre, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK.

Abstract

Chronic sleep disturbances, associated with cardiometabolic diseases, psychiatric disorders and all-cause mortality, affect 25-30% of adults worldwide. Although environmental factors contribute substantially to self-reported habitual sleep duration and disruption, these traits are heritable and identification of the genes involved should improve understanding of sleep, mechanisms linking sleep to disease and development of new therapies. We report single- and multiple-trait genome-wide association analyses of self-reported sleep duration, insomnia symptoms and excessive daytime sleepiness in the UK Biobank (n = 112,586). We discover loci associated with insomnia symptoms (near MEIS1, TMEM132E, CYCL1 and TGFBI in females and WDR27 in males), excessive daytime sleepiness (near AR-OPHN1) and a composite sleep trait (near PATJ (INADL) and HCRTR2) and replicate a locus associated with sleep duration (at PAX8). We also observe genetic correlation between longer sleep duration and schizophrenia risk (rg = 0.29, P = 1.90 × 10-13) and between increased levels of excessive daytime sleepiness and increased measures for adiposity traits (body mass index (BMI): rg = 0.20, P = 3.12 × 10-9; waist circumference: rg = 0.20, P = 2.12 × 10-7).

PMID:
27992416
PMCID:
PMC5491693
DOI:
10.1038/ng.3749
[Indexed for MEDLINE]
Free PMC Article

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