title: Genome-wide association analyses of sleep disturbance traits identify new loci and highlight shared genetics with neuropsychiatric and metabolic traits.
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).
authors.affiliation: Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts, USA.|Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.|Broad Institute, Cambridge, Massachusetts, USA.
authors.forename: Jacqueline M
authors.initials: JM
authors.lastname: Lane
authors.affiliation: Department of Epidemiology and Biostatistics, School of Medicine, Case Western Reserve University, Cleveland, Ohio, USA.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Liang
authors.affiliation: Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts, USA.|Broad Institute, Cambridge, Massachusetts, USA.
authors.forename: Irma
authors.initials: I
authors.lastname: Vlasac
authors.affiliation: Division of Cardiovascular Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.|George Institute for Global Health, University of Oxford, Oxford Martin School, Oxford, UK.
authors.forename: Simon G
authors.identifier: http://orcid.org/0000-0002-8896-073X
authors.initials: SG
authors.lastname: Anderson
authors.affiliation: Division of Endocrinology, Diabetes and Gastroenterology, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.
authors.forename: David A
authors.identifier: http://orcid.org/0000-0001-8676-8704
authors.initials: DA
authors.lastname: Bechtold
authors.affiliation: MRC Integrative Epidemiology Unit at the University of Bristol, Bristol, UK.|School of Social and Community Medicine, University of Bristol, Bristol, UK.
authors.forename: Jack
authors.initials: J
authors.lastname: Bowden
authors.affiliation: 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.
authors.forename: Richard
authors.initials: R
authors.lastname: Emsley
authors.affiliation: Broad Institute, Cambridge, Massachusetts, USA.
authors.forename: Shubhroz
authors.initials: S
authors.lastname: Gill
authors.affiliation: Engineering and Applied Science, Aston University, Birmingham, UK.|Media Laboratory, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
authors.forename: Max A
authors.initials: MA
authors.lastname: Little
authors.affiliation: Sleep and Circadian Neuroscience Institute, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK.
authors.forename: Annemarie I
authors.initials: AI
authors.lastname: Luik
authors.affiliation: Division of Endocrinology, Diabetes and Gastroenterology, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.
authors.forename: Andrew
authors.initials: A
authors.lastname: Loudon
authors.affiliation: Division of Sleep and Circadian Disorders, Brigham and Women's Hospital and Division of Sleep Medicine, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Frank A J L
authors.initials: FA
authors.lastname: Scheer
authors.affiliation: Broad Institute, Cambridge, Massachusetts, USA.|Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.|Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: Shaun M
authors.initials: SM
authors.lastname: Purcell
authors.affiliation: Sleep and Circadian Neuroscience Institute, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK.
authors.forename: Simon D
authors.initials: SD
authors.lastname: Kyle
authors.affiliation: MRC Integrative Epidemiology Unit at the University of Bristol, Bristol, UK.|School of Social and Community Medicine, University of Bristol, Bristol, UK.
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Lawlor
authors.affiliation: Department of Epidemiology and Biostatistics, School of Medicine, Case Western Reserve University, Cleveland, Ohio, USA.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Department of Medicine, Brigham and Women's Hospital and Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Susan
authors.initials: S
authors.lastname: Redline
authors.affiliation: Division of Endocrinology, Diabetes and Gastroenterology, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.
authors.forename: David W
authors.identifier: http://orcid.org/0000-0002-4739-6773
authors.initials: DW
authors.lastname: Ray
authors.affiliation: Division of Endocrinology, Diabetes and Gastroenterology, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.|Manchester Diabetes Centre, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK.
authors.forename: Martin K
authors.initials: MK
authors.lastname: Rutter
authors.affiliation: Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts, USA.|Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.|Broad Institute, Cambridge, Massachusetts, USA.|Division of Sleep and Circadian Disorders, Brigham and Women's Hospital and Division of Sleep Medicine, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Richa
authors.initials: R
authors.lastname: Saxena
mesh_terms: D050154:Adiposity / Q000235:genetics; D000328:Adult; D000368:Aged; D005260:Female; D056426:Genetic Loci / Q000235:genetics*; D055106:Genome-Wide Association Study / Q000379:methods; D006801:Humans; D008297:Male; D001523:Mental Disorders / Q000235:genetics*; D008659:Metabolic Diseases / Q000235:genetics*; D008875:Middle Aged; D010641:Phenotype; D057566:Self Report; D012890:Sleep / Q000235:genetics*; D012893:Sleep Wake Disorders / Q000235:genetics*; D055105:Waist Circumference / Q000235:genetics