Genome-wide association study identifies genetic loci for self-reported habitual sleep duration supported by accelerometer-derived estimates

Research output: Contribution to journalArticle

Authors

  • Hassan S. Dashti
  • Samuel E. Jones
  • Andrew R. Wood
  • Jacqueline M. Lane
  • Vincent T. Van Hees
  • Heming Wang
  • Jessica A. Rhodes
  • Yanwei Song
  • Krunal Patel
  • Simon G. Anderson
  • Robin N. Beaumont
  • David A. Bechtold
  • Jack Bowden
  • Brian E. Cade
  • Marta Garaulet
  • Simon D. Kyle
  • Andrew S. Loudon
  • Annemarie I. Luik
  • Frank A. J. L. Scheer
  • Kai Spiegelhalder
  • Jessica Tyrrell
  • Daniel J. Gottlieb
  • Henning Tiemeier
  • David W. Ray
  • Shaun M. Purcell
  • Timothy M. Frayling
  • Susan Redline
  • Deborah A. Lawlor
  • Martin K. Rutter
  • Michael N. Weedon
  • Richa Saxena

Colleges, School and Institutes

External organisations

  • Aston University
  • MIT

Abstract

Sleep is an essential state of decreased activity and alertness but molecular factors regulating sleep duration remain unknown. Through genome-wide association analysis in 446,118 adults of European ancestry from the UK Biobank, we identify 78 loci for self-reported habitual sleep duration (p < 5 × 10−8; 43 loci at p < 6 × 10−9). Replication is observed for PAX8, VRK2, and FBXL12/UBL5/PIN1 loci in the CHARGE study (n = 47,180; p < 6.3 × 10−4), and 55 signals show sign-concordant effects. The 78 loci further associate with accelerometer-derived sleep duration, daytime inactivity, sleep efficiency and number of sleep bouts in secondary analysis (n = 85,499). Loci are enriched for pathways including striatum and subpallium development, mechanosensory response, dopamine binding, synaptic neurotransmission and plasticity, among others. Genetic correlation indicates shared links with anthropometric, cognitive, metabolic, and psychiatric traits and two-sample Mendelian randomization highlights a bidirectional causal link with schizophrenia. This work provides insights into the genetic basis for inter-individual variation in sleep duration implicating multiple biological pathways.

Details

Original languageEnglish
Article number1100
Number of pages12
JournalNature Communications
Volume10
Issue number1
Publication statusPublished - 7 Mar 2019

Keywords

  • Accelerometry, Adult, Aged, European Continental Ancestry Group, Female, Genetic Loci, Genome-Wide Association Study, Humans, Linkage Disequilibrium, Male, Middle Aged, Polymorphism, Single Nucleotide, Schizophrenia/genetics, Self Report, Sleep/genetics, United Kingdom