Genome-wide association analysis of self-reported daytime sleepiness identifies 42 loci that suggest biological subtypes
Wang, Heming; Lane, Jacqueline M.; Jones, Samuel E.; Dashti, Hassan S.; Ollila, Hanna M.; Wood, Andrew R.; van Hees, Vincent T.; Brumpton, Ben Michael; Winsvold, Bendik K 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.; 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
Journal article, Peer reviewed
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Original versionNature Communications. 2019, 10:3503 1-12. 10.1038/s41467-019-11456-7
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.