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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.

SUBMITTER: Wang H 

PROVIDER: S-EPMC6692391 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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

Wang Heming H   Lane Jacqueline M JM   Jones Samuel E SE   Dashti Hassan S HS   Ollila Hanna M HM   Wood Andrew R AR   van Hees Vincent T VT   Brumpton Ben B   Winsvold Bendik S BS   Kantojärvi Katri K   Palviainen Teemu T   Cade Brian E BE   Sofer Tamar T   Song Yanwei Y   Patel Krunal K   Anderson Simon G SG   Bechtold David A DA   Bowden Jack J   Emsley Richard R   Kyle Simon D SD   Little Max A MA   Loudon Andrew S AS   Scheer Frank A J L FAJL   Purcell Shaun M SM   Richmond Rebecca C RC   Spiegelhalder Kai K   Tyrrell Jessica J   Zhu Xiaofeng X   Hublin Christer C   Kaprio Jaakko A JA   Kristiansson Kati K   Sulkava Sonja S   Paunio Tiina T   Hveem Kristian K   Nielsen Jonas B JB   Willer Cristen J CJ   Zwart John-Anker JA   Strand Linn B LB   Frayling Timothy M TM   Ray David D   Lawlor Deborah A DA   Rutter Martin K MK   Weedon Michael N MN   Redline Susan S   Saxena Richa R  

Nature communications 20190813 1

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  ...[more]

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