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

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.

Publication DOI: https://doi.org/10.1038/s41467-019-11456-7
Divisions: Engineering & Applied Sciences > Mathematics
Engineering & Applied Sciences > Systems analytics research institute (SARI)
Engineering & Applied Sciences
Additional Information: © The Author(s) 2019. Open Access - This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/ licenses/by/4.0/.
Uncontrolled Keywords: sleep,sleep disorders,genome-wide association,Physics and Astronomy(all),Chemistry(all),Biochemistry, Genetics and Molecular Biology(all)
Full Text Link:
Related URLs: http://www.natu ... 467-019-11456-7 (Publisher URL)
http://www.scop ... tnerID=8YFLogxK (Scopus URL)
PURE Output Type: Article
Published Date: 2019-08-13
Accepted Date: 2019-06-27
Authors: Wang, Heming
Lane, Jacqueline M.
Jones, Samuel E.
Dashti, Hassan S.
Ollila, Hanna M.
Wood, Andrew R.
Van Hees, Vincent T.
Brumpton, Ben
Winsvold, Bendik S.
Kantojärvi, Katri
Palviainen, Teemu
Cade, Brian E.
Sofer, Tamar
Song, Yanwei
Patel, Krunal
Anderson, Simon G.
Bechtold, David A.
Bowden, Jack
Emsley, Richard
Kyle, Simon D.
Little, Max A. ( 0000-0002-1507-3822)
Loudon, Andrew S.
Scheer, Frank A. J. L.
Purcell, Shaun M.
Richmond, Rebecca C.
Spiegelhalder, Kai
Tyrrell, Jessica
Zhu, Xiaofeng
Hublin, Christer
Kaprio, Jaakko A.
Kristiansson, Kati
Sulkava, Sonja
Paunio, Tiina
Hveem, Kristian
Nielsen, Jonas B.
Willer, Cristen J.
Zwart, John-anker
Strand, Linn B.
Frayling, Timothy M.
Ray, David
Lawlor, Deborah A.
Rutter, Martin K.
Weedon, Michael N.
Redline, Susan
Saxena, Richa

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