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

Research output: Contribution to journalArticle

Authors

  • 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
  • Brian E. Cade
  • Tamar Sofer
  • Yanwei Song
  • Krunal Patel
  • Simon G. Anderson
  • David A. Bechtold
  • Jack Bowden
  • Richard Emsley
  • Simon D. Kyle
  • Andrew S. Loudon
  • Frank A.J.L. Scheer
  • Shaun M. Purcell
  • Rebecca C. Richmond
  • Kai Spiegelhalder
  • Jessica Tyrrell
  • Xiaofeng Zhu
  • Christer Hublin
  • Jaakko A. Kaprio
  • Kati Kristiansson
  • Sonja Sulkava
  • Tiina Paunio
  • Kristian Hveem
  • Jonas B. Nielsen
  • Cristen J. Willer
  • John Anker Zwart
  • Linn B. Strand
  • Timothy M. Frayling
  • David Ray
  • Deborah A. Lawlor
  • Martin K. Rutter
  • Michael N. Weedon
  • Susan Redline
  • Richa Saxena

Colleges, School and Institutes

External organisations

  • BRIGHAM AND WOMEN'S HOSPITAL
  • Broad Institute
  • Harvard Medical School, Wellman Center for Photomedicine, Massachusetts General Hospital
  • University of Exeter
  • Stanford University
  • University of Helsinki
  • Netherlands eScience Center
  • Norwegian University of Science and Technology
  • BRISTOL UNIVERSITY
  • St. Olavs Hospital
  • Oslo University Hospital
  • National Institute for Health and Welfare
  • Helsinki University Hospital
  • Northeastern University
  • University of Manchester
  • University of the West Indies
  • OXFORD UNIVERSITY
  • University of Freiburg
  • Department of Astronomy, Case Western Reserve University
  • University of Michigan Medical School
  • John Radcliffe Hospital
  • Manchester University NHS Foundation Trust
  • Beth Israel Deaconess Medical Center
  • Aston University
  • Massachusetts Institute of Technology, Cambridge, MA, USA

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.

Details

Original languageEnglish
Article number3503
Number of pages12
JournalNature Communications
Volume10
Publication statusPublished - 13 Aug 2019