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

Jacqueline M. Lane, Jingjing Liang, Irma Vlasac, Simon G. Anderson, David A. Bechtold, Jack Bowden, Richard Emsley, Shubhroz Gill, Max A. Little, AnneMarie I. Luik, Andrew Loudon, Frank A.J.L. Scheer, Shaun M. Purcell, Simon D. Kyle, Deborah A. Lawlor, Xiaofeng Zhu, Susan Redline, David W. Ray, Martin K. Rutter, Richa Saxena
doi: https://doi.org/10.1101/082792
Jacqueline M. Lane
1Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA, USA
2Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
3Broad Institute, Cambridge, MA, USA
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Jingjing Liang
4Department of Epidemiology and Biostatistics, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA.
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Irma Vlasac
1Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA, USA
3Broad Institute, Cambridge, MA, USA
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Simon G. Anderson
5Division of Cardiovascular Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, UK
6The George Institute for Global Health, University of Oxford, Oxford Martin School, 34 Broad Street Oxford OX1 3BD, UK
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David A. Bechtold
7Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK
8Division of Endocrinology, Diabetes & Gastroenterology, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, UK
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Jack Bowden
9MRC Integrative Epidemiology Unit at the University of Bristol, Bristol, UK
10School of Social and Community Medicine, University of Bristol, Bristol, UK
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Richard Emsley
11Division 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
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Shubhroz Gill
3Broad Institute, Cambridge, MA, USA
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Max A. Little
12Engineering and Applied Science, Aston University, Birmingham, UK
13Media Lab, Massachusetts Institute of Technology, Cambridge, MA, USA
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AnneMarie I. Luik
14Sleep and Circadian Neuroscience Institute, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK
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Andrew Loudon
7Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK
8Division of Endocrinology, Diabetes & Gastroenterology, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, UK
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Frank A.J.L. Scheer
15Division of Sleep and Circadian Disorders, Brigham and Women’s Hospital, and Division of Sleep Medicine, Harvard Medical School, Boston, MA, USA
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Shaun M. Purcell
3Broad Institute, Cambridge, MA, USA
16Department of Psychiatry, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA.
17Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York.
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Simon D. Kyle
14Sleep and Circadian Neuroscience Institute, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK
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Deborah A. Lawlor
9MRC Integrative Epidemiology Unit at the University of Bristol, Bristol, UK
10School of Social and Community Medicine, University of Bristol, Bristol, UK
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Xiaofeng Zhu
4Department of Epidemiology and Biostatistics, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA.
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Susan Redline
18Departments of Medicine, Brigham and Women's Hospital and Beth Israel Deaconess Medical Center, Harvard Medical School, Boston
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David W. Ray
7Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK
8Division of Endocrinology, Diabetes & Gastroenterology, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, UK
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Martin K. Rutter
7Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK
8Division of Endocrinology, Diabetes & Gastroenterology, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, UK
19Manchester Diabetes Centre, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK
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Richa Saxena
1Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA, USA
2Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
3Broad Institute, Cambridge, MA, USA
15Division of Sleep and Circadian Disorders, Brigham and Women’s Hospital, and Division of Sleep Medicine, Harvard Medical School, Boston, MA, USA
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Abstract

Chronic sleep disturbances, associated with cardio-metabolic diseases, psychiatric disorders and all-cause mortality1,2, affect 25–30% of adults worldwide3. While environmental factors contribute importantly to self-reported habitual sleep duration and disruption, these traits are heritable4–9, and gene identification should improve our understanding of sleep function, mechanisms linking sleep to disease, and development of novel therapies. We report single and multi-trait genome-wide association analyses (GWAS) of self-reported sleep duration, insomnia symptoms including difficulty initiating and/or maintaining sleep, and excessive daytime sleepiness in the UK Biobank (n=112,586), with discovery of loci for insomnia symptoms (near MEIS1, TMEM132E, CYCL1, TGFBI in females and WDR27 in males), excessive daytime sleepiness (near AR/OPHN1) and a composite sleep trait (near INADL and HCRTR2), as well as replication of a locus for sleep duration (at PAX-8). Genetic correlation was observed between longer sleep duration and schizophrenia (rG=0.29, p=1.90x10−13) and between increased excessive daytime sleepiness and increased adiposity traits (BMI rG=0.20, p=3.12x10−09; waist circumference rG=0.20, p=2.12x10−07).

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Posted October 24, 2016.
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Genome-wide association analyses of sleep disturbance traits identify new loci and highlight shared genetics with neuropsychiatric and metabolic traits
Jacqueline M. Lane, Jingjing Liang, Irma Vlasac, Simon G. Anderson, David A. Bechtold, Jack Bowden, Richard Emsley, Shubhroz Gill, Max A. Little, AnneMarie I. Luik, Andrew Loudon, Frank A.J.L. Scheer, Shaun M. Purcell, Simon D. Kyle, Deborah A. Lawlor, Xiaofeng Zhu, Susan Redline, David W. Ray, Martin K. Rutter, Richa Saxena
bioRxiv 082792; doi: https://doi.org/10.1101/082792
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Genome-wide association analyses of sleep disturbance traits identify new loci and highlight shared genetics with neuropsychiatric and metabolic traits
Jacqueline M. Lane, Jingjing Liang, Irma Vlasac, Simon G. Anderson, David A. Bechtold, Jack Bowden, Richard Emsley, Shubhroz Gill, Max A. Little, AnneMarie I. Luik, Andrew Loudon, Frank A.J.L. Scheer, Shaun M. Purcell, Simon D. Kyle, Deborah A. Lawlor, Xiaofeng Zhu, Susan Redline, David W. Ray, Martin K. Rutter, Richa Saxena
bioRxiv 082792; doi: https://doi.org/10.1101/082792

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