Genetic Epidemiology, Translational Neurogenomics, Psychiatric Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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27142678
TITLE
Genetic variants in RBFOX3 are associated with sleep latency.
ABSTRACT
NlmCategory: UNASSIGNED
Time to fall asleep (sleep latency) is a major determinant of sleep quality. Chronic, long sleep latency is a major characteristic of sleep-onset insomnia and/or delayed sleep phase syndrome. In this study we aimed to discover common polymorphisms that contribute to the genetics of sleep latency. We performed a meta-analysis of genome-wide association studies (GWAS) including 2 572 737 single nucleotide polymorphisms (SNPs) established in seven European cohorts including 4242 individuals. We found a cluster of three highly correlated variants (rs9900428, rs9907432 and rs7211029) in the RNA-binding protein fox-1 homolog 3 gene (RBFOX3) associated with sleep latency (P-values=5.77 × 10(-08), 6.59 × 10(-)(08) and 9.17 × 10(-)(08)). These SNPs were replicated in up to 12 independent populations including 30 377 individuals (P-values=1.5 × 10(-)(02), 7.0 × 10(-)(03) and 2.5 × 10(-)(03); combined meta-analysis P-values=5.5 × 10(-07), 5.4 × 10(-07) and 1.0 × 10(-07)). A functional prediction of RBFOX3 based on co-expression with other genes shows that this gene is predominantly expressed in brain (P-value=1.4 × 10(-316)) and the central nervous system (P-value=7.5 × 10(-)(321)). The predicted function of RBFOX3 based on co-expression analysis with other genes shows that this gene is significantly involved in the release cycle of neurotransmitters including gamma-aminobutyric acid and various monoamines (P-values<2.9 × 10(-11)) that are crucial in triggering the onset of sleep. To conclude, in this first large-scale GWAS of sleep latency we report a novel association of variants in RBFOX3 gene. Further, a functional prediction of RBFOX3 supports the involvement of RBFOX3 with sleep latency.European Journal of Human Genetics advance online publication, 4 May 2016; doi:10.1038/ejhg.2016.31.
DATE PUBLISHED
2016 May 4
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2015/08/18
revised 2016/01/13
accepted 2016/02/01
entrez 2016/05/05 06:00
pubmed 2016/05/05 06:00
medline 2016/05/05 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Amin N Amin Najaf N Unit of Genetic Epidemiology, Department of Epidemiology, Erasmus University Medical Centre, Rotterdam, The Netherlands.
Allebrandt KV Allebrandt Karla V KV Institute of Medical Psychology, Ludwig-Maximilians-University, Munich, Germany.
van der Spek A van der Spek Ashley A Unit of Genetic Epidemiology, Department of Epidemiology, Erasmus University Medical Centre, Rotterdam, The Netherlands.
Müller-Myhsok B Müller-Myhsok Bertram B Max-Planck-Institute of Psychiatry, Munich, Germany.
Hek K Hek Karin K Department of Psychiatry, Erasmus Medical Center, Rotterdam, The Netherlands.
Teder-Laving M Teder-Laving Maris M Estonian Genome Center, University of Tartu and Estonian Biocenter, Tartu, Estonia.
Hayward C Hayward Caroline C Medical Research Council, Human Genetics Unit, IGMM, University of Edinburgh, Edinburgh, Scotland.
Esko T Esko Tõnu T Estonian Genome Center, University of Tartu and Estonian Biocenter, Tartu, Estonia.
van Mill JG van Mill Josine G JG Department of Psychiatry, VU University Medical Center Amsterdam, Amsterdam, The Netherlands.
Mbarek H Mbarek Hamdi H Department of Biological Psychology, VU University, Amsterdam, The Netherlands.
Watson NF Watson Nathaniel F NF University of Washington Medicine Sleep Center, Seattle, WA, USA.
Melville SA Melville Scott A SA Department of Medicine (Biomedical Genetics), Boston University School of Medicine, Boston, MA, USA.
Del Greco FM Del Greco Fabiola M FM Center for Biomedicine, European Academy of Bolzano, Bolzano, Italy - Affiliated Institute of the University of Lübeck, Lübeck, Germany.
Byrne EM Byrne Enda M EM Queensland Institute of Medical Research, Brisbane, QLD, Australia.
Oole E Oole Edwin E Center for Biomics, Erasmus Medical Center, Rotterdam, The Netherlands.
Kolcic I Kolcic Ivana I School of Medicine, University of Split, Split, Croatia.
Chen TH Chen Ting-Hsu TH VA Boston Healthcare System, Boston University, Boston, MA, USA.
Evans DS Evans Daniel S DS California Pacific Medical Center Research Institute, San Francisco, CA, USA.
Coresh J Coresh Josef J Departments of Epidemiology, Biostatistics, and Medicine, Johns Hopkins University, Baltimore, MD, USA.
Vogelzangs N Vogelzangs Nicole N Department of Psychiatry, VU University Medical Center Amsterdam, Amsterdam, The Netherlands.
Karjalainen J Karjalainen Juha J Department of Genetics, University Medical Center Groningen and University of Groningen, Groningen, The Netherlands.
Willemsen G Willemsen Gonneke G Department of Biological Psychology, VU University, Amsterdam, The Netherlands.
Gharib SA Gharib Sina A SA Department of Medicine, Division of Pulmonary & Critical Care Medicine, University of Washington, Seattle, WA, USA.
Zgaga L Zgaga Lina L Medical Research Council, Human Genetics Unit, IGMM, University of Edinburgh, Edinburgh, Scotland.
Mihailov E Mihailov Evelin E Estonian Genome Center, University of Tartu and Estonian Biocenter, Tartu, Estonia.
Stone KL Stone Katie L KL California Pacific Medical Center Research Institute, San Francisco, CA, USA.
Campbell H Campbell Harry H Centre for Global Health Research, Usher Institute for Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, Scotland.
Brouwer RW Brouwer Rutger Ww RW Center for Biomics, Erasmus Medical Center, Rotterdam, The Netherlands.
Demirkan A Demirkan Ayse A Unit of Genetic Epidemiology, Department of Epidemiology, Erasmus University Medical Centre, Rotterdam, The Netherlands.
Isaacs A Isaacs Aaron A Unit of Genetic Epidemiology, Department of Epidemiology, Erasmus University Medical Centre, Rotterdam, The Netherlands.
Dogas Z Dogas Zoran Z Department of Neuroscience and Sleep Medicine Centre, University of Split School of Medicine, Split, Croatia.
Marciante KD Marciante Kristin D KD Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, USA.
Campbell S Campbell Susan S Medical Research Council, Human Genetics Unit, IGMM, University of Edinburgh, Edinburgh, Scotland.
Borovecki F Borovecki Fran F Centre for Functional Genomics and Department of Neurology, Faculty of Medicine, University of Zagreb, Zagreb, Croatia.
Luik AI Luik Annemarie I AI Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands.
Li M Li Man M Department of Epidemiology, Johns Hopkins University, Baltimore, MD, USA.
Hottenga JJ Hottenga Jouke Jan JJ Department of Biological Psychology, VU University, Amsterdam, The Netherlands.
Huffman JE Huffman Jennifer E JE Medical Research Council, Human Genetics Unit, IGMM, University of Edinburgh, Edinburgh, Scotland.
van den Hout MC van den Hout Mirjam Cgn MC Center for Biomics, Erasmus Medical Center, Rotterdam, The Netherlands.
Cummings SR Cummings Steven R SR California Pacific Medical Center Research Institute, San Francisco, CA, USA.
Aulchenko YS Aulchenko Yurii S YS Unit of Genetic Epidemiology, Department of Epidemiology, Erasmus University Medical Centre, Rotterdam, The Netherlands.
Gehrman PR Gehrman Philip R PR Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, USA.
Uitterlinden AG Uitterlinden André G AG Netherlands Consortium for Healthy Ageing and National Genomics Initiative, Leiden, The Netherlands.
Wichmann HE Wichmann Heinz-Erich HE Institute of Medical Statistics and Epidemiology, Technical University Munich, Munich, Germany.
Müller-Nurasyid M Müller-Nurasyid Martina M DZHK (German Centre for Cardiovascular Research), Partner Site Munich Heart Alliance, Munich, Germany.
Fehrmann RS Fehrmann Rudolf Sn RS Department of Genetics, University Medical Center Groningen and University of Groningen, Groningen, The Netherlands.
Montgomery GW Montgomery Grant W GW Queensland Institute of Medical Research, Brisbane, QLD, Australia.
Hofman A Hofman Albert A Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Kao WH Kao Wen Hong Linda WH Department of Epidemiology, Johns Hopkins University, Baltimore, MD, USA.
Oostra BA Oostra Ben A BA Unit of Genetic Epidemiology, Department of Epidemiology, Erasmus University Medical Centre, Rotterdam, The Netherlands.
Wright AF Wright Alan F AF Medical Research Council, Human Genetics Unit, IGMM, University of Edinburgh, Edinburgh, Scotland.
Vink JM Vink Jacqueline M JM Department of Biological Psychology, VU University, Amsterdam, The Netherlands.
Wilson JF Wilson James F JF Centre for Global Health Research, Usher Institute for Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, Scotland.
Pramstaller PP Pramstaller Peter P PP Department of Neurology, University of Lübeck, Lübeck, Germany.
Hicks AA Hicks Andrew A AA Center for Biomedicine, European Academy of Bolzano, Bolzano, Italy - Affiliated Institute of the University of Lübeck, Lübeck, Germany.
Polasek O Polasek Ozren O Centre for Global Health, University of Split School of Medicine, Split, Croatia.
Punjabi NM Punjabi Naresh M NM Department of Pulmonary Medicine and Epidemiology, Johns Hopkins University, Baltimore, MD, USA.
Redline S Redline Susan S Department of Medicine, Brigham and Women's Hospital and Beth Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Psaty BM Psaty Bruce M BM Group Health Research Institute, Group Health Cooperative, Seattle, WA, USA.
Heath AC Heath Andrew C AC Department of Psychiatry, Washington University, St Louis, MO, USA.
Merrow M Merrow Martha M Institute of Medical Psychology, Ludwig-Maximilians-University, Munich, Germany.
Tranah GJ Tranah Gregory J GJ California Pacific Medical Center Research Institute, San Francisco, CA, USA.
Gottlieb DJ Gottlieb Daniel J DJ VA Boston Healthcare System, Boston, MA, USA.
Boomsma DI Boomsma Dorret I DI Department of Biological Psychology, VU University, Amsterdam, The Netherlands.
Martin NG Martin Nicholas G NG Queensland Institute of Medical Research, Brisbane, QLD, Australia.
Rudan I Rudan Igor I Centre for Global Health Research, Usher Institute for Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, Scotland.
Tiemeier H Tiemeier Henning H Department of Child and Adolescent Psychiatry, Erasmus MC, Rotterdam, The Netherlands.
van IJcken WF van IJcken Wilfred Fj WF Center for Biomics, Erasmus Medical Center, Rotterdam, The Netherlands.
Penninx BW Penninx Brenda W BW Department of Psychiatry, VU University Medical Center Amsterdam, Amsterdam, The Netherlands.
Metspalu A Metspalu Andres A Estonian Genome Center, University of Tartu and Estonian Biocenter, Tartu, Estonia.
Meitinger T Meitinger Thomas T Institute of Human Genetics, Techinsche Universität München, München, Germany.
Franke L Franke Lude L Department of Genetics, University Medical Center Groningen and University of Groningen, Groningen, The Netherlands.
Roenneberg T Roenneberg Till T Institute of Medical Psychology, Ludwig-Maximilians-University, Munich, Germany.
van Duijn CM van Duijn Cornelia M CM Centre for Medical Systems Biology, Leiden, The Netherlands.
INVESTIGATORS
JOURNAL
VOLUME:
ISSUE:
TITLE: European journal of human genetics : EJHG
ISOABBREVIATION: Eur. J. Hum. Genet.
YEAR: 2016
MONTH: May
DAY: 4
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1476-5438
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Eur J Hum Genet
COUNTRY: England
ISSNLINKING: 1018-4813
NLMUNIQUEID: 9302235
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