Genome-wide association analysis of self-reported daytime sleepiness identifies 42 loci that suggest biological subtypes.
Heming WangJacqueline M LaneSamuel E JonesHassan S DashtiHanna M OllilaAndrew R WoodVincent Theodoor van HeesBen Michael BrumptonBendik Slagsvold WinsvoldKatri KantojärviTeemu PalviainenBrian E CadeTamar SoferYanwei SongKrunal PatelSimon George AndersonDavid A BechtoldJack BowdenRichard EmsleySimon D KyleMax A LittleAndrew S LoudonFrank A J L ScheerShaun M PurcellRebecca C RichmondKai SpiegelhalderJessica TyrrellXiaofeng ZhuChrister HublinJaakko A KaprioKati KristianssonSonja SulkavaTiina PaunioKristian HveemJonas B NielsenCristen J WillerJohn-Anker ZwartLinn B StrandTimothy M FraylingDavid RayDeborah A LawlorMartin K RutterMichael N WeedonSusan RedlineRicha SaxenaPublished in: Nature communications (2019)
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.
Keyphrases
- sleep quality
- genome wide
- depressive symptoms
- physical activity
- obstructive sleep apnea
- genome wide association
- dna methylation
- copy number
- gene expression
- metabolic syndrome
- type diabetes
- mental health
- multiple sclerosis
- weight gain
- body mass index
- adipose tissue
- cross sectional
- resting state
- functional connectivity
- brain injury