Genome-wide association analysis of self-reported daytime sleepiness identifies 42 loci that suggest biological subtypes
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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 , Kyle , S D , Little , M A , Loudon , A S , Scheer , F A J L , Purcell , S M , Richmond , R C , Spiegelhalder , K , Tyrrell , J , Zhu , X , Hublin , C , Kaprio , J A , Kristiansson , K , Sulkava , S , Paunio , T , Hveem , K , Nielsen , J B , Willer , C J , Zwart , J A , Strand , L B , Frayling , T M , Ray , D , Lawlor , D A , Rutter , M K , Weedon , M N , Redline , S & Saxena , R 2019 , ' Genome-wide association analysis of self-reported daytime sleepiness identifies 42 loci that suggest biological subtypes ' , Nature Communications , vol. 10 , no. 1 , 3503 . https://doi.org/10.1038/s41467-019-11456-7 , https://doi.org/10.1038/s41467-019-11456-7
| Title: | Genome-wide association analysis of self-reported daytime sleepiness identifies 42 loci that suggest biological subtypes |
| Author: | 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.; 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 |
| Contributor organization: | Institute for Molecular Medicine Finland University of Helsinki Department of Medical and Clinical Genetics Technology Centre Genetic Epidemiology Department of Public Health Centre of Excellence in Complex Disease Genetics Doctoral Programme Brain & Mind Doctoral Programme in Clinical Research Doctoral Programme in Population Health Jaakko Kaprio / Principal Investigator Quantitative Genetics Doctoral Programme in Biomedicine Clinicum Department of Psychiatry Doctoral Programme in Integrative Life Science HUS Psychiatry |
| Date: | 2019-08-13 |
| Language: | eng |
| Number of pages: | 12 |
| Belongs to series: | Nature Communications |
| ISSN: | 2041-1723 |
| DOI: | https://doi.org/10.1038/s41467-019-11456-7 |
| URI: | http://hdl.handle.net/10138/306350 |
| 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. |
| Description: | Funding Information: This research has been conducted using the UK Biobank Resource under applications 6818 and 9072. We would like to thank the participants and researchers from the UK Biobank who contributed or collected data. This work was supported by US NIH grants R01DK107859 (to R.S.), R01HL113338 (to S.R.), R35HL135818 (to S.R.), R01DK102696 (to F.S. and R.S), R01DK105072 (to R.S. and F.S.), F32DK102323 (to JML), T32HL007567(to J.M.L), K01HL135405 (to B.E.C.), R01HL127564 (to C.J.W.), R35HL135824 (to C.J.W.), and HG003054 (to X.Z.); Sleep Research Society Foundation Career Development Award 018-JP-18 (to H.W.); American Thoracic Society Foundation Unrestricted Grant (to B.E.C.); Phyllis and Jerome Lyle Rappaport MGH Research Scholar Award (to R.S.); UK Medical Research Council MC_UU_00011/3, MC_UU_00011/6, and MR/M005070/1 (to J.B., D.A.L., and M.N.W.); UK National Institute of Health Research NF-SI-0611-10196 (to D.A.L.); Diabetes UK grant 17/ 000570 (to M.K.R., D.A.L., and M.N.W.); the Wellcome Trust Investigator Award 107849/Z/15/Z (to D.R.); Academy of Finland #309643 (to H.M.O.); Stiftelsen Kristian Gerhard Jebsen grant (to K.H.); Research Council of Norway #231187/F20 (to B.W.); the Liaison Committee for education, research and innovation in Central Norway grant (to B.B.); the Joint Research Committee between St. Olavs hospital and the Faculty of Medicine and Health Sciences, NTNU (to K.H.); the Danish Heart Foundation 16-R107-A6779 (to J.B.N.), and the Lundbeck Foundation R220-2016-1434 (to J.B.N.). Academy of Finland grant 290039 (to T.P.). J.K. has been supported by the Academy of Finland (grants 265240, 263278, 308248, 312073). Publisher Copyright: © 2019, The Author(s). |
| Subject: |
RESTLESS LEGS
GENETIC INFLUENCES OBESITY HERITABILITY WAKEFULNESS DISEASE APNEA RISK DISTURBANCE IMPAIRMENT 3112 Neurosciences |
| Peer reviewed: | Yes |
| Rights: | cc_by |
| Usage restriction: | openAccess |
| Self-archived version: | publishedVersion |
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