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

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. KyleMax A. Little, 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

Research output: Contribution to journalArticle

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.
Original languageEnglish
Article number3503
JournalNature Communications
Volume10
Issue number1
DOIs
Publication statusPublished - 13 Aug 2019

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Keywords

  • sleep
  • sleep disorders
  • genome-wide association

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    Wang, H., Lane, J. M., Jones, S. E., Dashti, H. S., Ollila, H. M., Wood, A. R., Van Hees, V. T., Brumpton, B., Winsvold, B. S., Kantojärvi, K., Palviainen, T., Cade, B. E., Sofer, T., Song, Y., Patel, K., Anderson, S. G., Bechtold, D. A., Bowden, J., Emsley, R., ... Saxena, R. (2019). Genome-wide association analysis of self-reported daytime sleepiness identifies 42 loci that suggest biological subtypes. Nature Communications, 10(1), [3503]. https://doi.org/10.1038/s41467-019-11456-7