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Genome-wide association analysis of self-reported daytime sleepiness identifies 42 loci that suggest biological subtypes

Author

Listed:
  • Heming Wang

    (Brigham and Women’s Hospital and Harvard Medical School
    Broad Institute)

  • Jacqueline M. Lane

    (Broad Institute
    Massachusetts General Hospital
    Massachusetts General Hospital and Harvard Medical School)

  • Samuel E. Jones

    (University of Exeter Medical School)

  • Hassan S. Dashti

    (Broad Institute
    Massachusetts General Hospital
    Massachusetts General Hospital and Harvard Medical School)

  • Hanna M. Ollila

    (Broad Institute
    Massachusetts General Hospital
    Stanford University
    University of Helsinki)

  • Andrew R. Wood

    (University of Exeter Medical School)

  • Vincent T. van Hees

    (Netherlands eScience Center)

  • Ben Brumpton

    (Norwegian University of Science and Technology
    MRC Integrative Epidemiology Unit at the University of Bristol
    Trondheim University Hospital)

  • Bendik S. Winsvold

    (Norwegian University of Science and Technology
    Oslo University Hospital and University of Oslo)

  • Katri Kantojärvi

    (National Institute for Health and Welfare
    University of Helsinki and Helsinki University Central Hospital)

  • Teemu Palviainen

    (HiLIFE, University of Helsinki)

  • Brian E. Cade

    (Brigham and Women’s Hospital and Harvard Medical School
    Broad Institute)

  • Tamar Sofer

    (Brigham and Women’s Hospital and Harvard Medical School
    Broad Institute)

  • Yanwei Song

    (Massachusetts General Hospital
    Northeastern University College of Science)

  • Krunal Patel

    (Massachusetts General Hospital
    Northeastern University College of Science)

  • Simon G. Anderson

    (The University of Manchester
    University of the West Indies)

  • David A. Bechtold

    (University of Manchester)

  • Jack Bowden

    (MRC Integrative Epidemiology Unit at the University of Bristol
    University of Bristol)

  • Richard Emsley

    (University of Manchester)

  • Simon D. Kyle

    (University of Oxford)

  • Max A. Little

    (Aston University
    Massachusetts Institute of Technology)

  • Andrew S. Loudon

    (University of Manchester)

  • Frank A. J. L. Scheer

    (Brigham and Women’s Hospital and Harvard Medical School
    Broad Institute)

  • Shaun M. Purcell

    (Brigham and Women’s Hospital and Harvard Medical School
    Broad Institute)

  • Rebecca C. Richmond

    (MRC Integrative Epidemiology Unit at the University of Bristol
    University of Bristol)

  • Kai Spiegelhalder

    (University of Freiburg)

  • Jessica Tyrrell

    (University of Exeter Medical School)

  • Xiaofeng Zhu

    (Case Western Reserve University)

  • Christer Hublin

    (HiLIFE, University of Helsinki
    University of Helsinki)

  • Jaakko A. Kaprio

    (HiLIFE, University of Helsinki
    University of Helsinki)

  • Kati Kristiansson

    (National Institute for Health and Welfare)

  • Sonja Sulkava

    (National Institute for Health and Welfare
    University of Helsinki and Helsinki University Central Hospital)

  • Tiina Paunio

    (National Institute for Health and Welfare
    University of Helsinki and Helsinki University Central Hospital)

  • Kristian Hveem

    (Norwegian University of Science and Technology
    MRC Integrative Epidemiology Unit at the University of Bristol)

  • Jonas B. Nielsen

    (University of Michigan)

  • Cristen J. Willer

    (University of Michigan)

  • John-Anker Zwart

    (Oslo University Hospital and University of Oslo)

  • Linn B. Strand

    (Norwegian University of Science and Technology)

  • Timothy M. Frayling

    (University of Exeter Medical School)

  • David Ray

    (John Radcliffe Hospital)

  • Deborah A. Lawlor

    (MRC Integrative Epidemiology Unit at the University of Bristol
    University of Bristol)

  • Martin K. Rutter

    (University of Manchester
    Manchester Academic Health Science Centre)

  • Michael N. Weedon

    (University of Exeter Medical School)

  • Susan Redline

    (Brigham and Women’s Hospital and Harvard Medical School
    Broad Institute
    Beth Israel Deaconess Medical Center)

  • Richa Saxena

    (Brigham and Women’s Hospital and Harvard Medical School
    Broad Institute
    Massachusetts General Hospital
    Massachusetts General Hospital and Harvard Medical School)

Abstract

Excessive daytime sleepiness (EDS) affects 10–20% of the population and is associated with substantial functional deficits. Here, we identify 42 loci for self-reported daytime sleepiness in GWAS of 452,071 individuals from the UK Biobank, with enrichment for genes expressed in brain tissues and in neuronal transmission pathways. We confirm the aggregate effect of a genetic risk score of 42 SNPs on daytime sleepiness in independent Scandinavian cohorts and on other sleep disorders (restless legs syndrome, insomnia) and sleep traits (duration, chronotype, accelerometer-derived sleep efficiency and daytime naps or inactivity). However, individual daytime sleepiness signals vary in their associations with objective short vs long sleep, and with markers of sleep continuity. The 42 sleepiness variants primarily cluster into two predominant composite biological subtypes - sleep propensity and sleep fragmentation. Shared genetic links are also seen with obesity, coronary heart disease, psychiatric diseases, cognitive traits and reproductive ageing.

Suggested Citation

  • Heming Wang & Jacqueline M. Lane & Samuel E. Jones & Hassan S. Dashti & Hanna M. Ollila & Andrew R. Wood & Vincent T. van Hees & Ben Brumpton & Bendik S. Winsvold & Katri Kantojärvi & Teemu Palviainen, 2019. "Genome-wide association analysis of self-reported daytime sleepiness identifies 42 loci that suggest biological subtypes," Nature Communications, Nature, vol. 10(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-11456-7
    DOI: 10.1038/s41467-019-11456-7
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