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

被引：149

作者：

Wang, Heming ^{[1
,2
,3
]}

Lane, Jacqueline M. ^{[2
,3
,4
,5
]}

Jones, Samuel E. ^{[6
]}

Dashti, Hassan S. ^{[2
,3
,4
,5
]}

Ollila, Hanna M. ^{[3
,4
,7
,8
]}

Wood, Andrew R. ^{[6
]}

van Hees, Vincent T. ^{[9
]}

Brumpton, Ben ^{[10
,11
,12
]}

Winsvold, Bendik S. ^{[10
,13
,14
]}

Kantojarvi, Katri ^{[15
,16
,17
,18
]}

Palviainen, Teemu ^{[19
]}

Cade, Brian E. ^{[1
,2
,3
]}

Sofer, Tamar ^{[1
,2
,3
]}

Song, Yanwei ^{[4
,20
]}

Patel, Krunal ^{[4
,20
]}

Anderson, Simon G. ^{[21
,22
]}

Bechtold, David A. ^{[23
]}

Bowden, Jack ^{[11
,24
]}

Emsley, Richard ^{[23
]}

Kyle, Simon D. ^{[25
]}

Little, Max A. ^{[26
,27
]}

Loudon, Andrew S. ^{[23
]}

Scheer, Frank A. J. L. ^{[1
,2
,3
]}

Purcell, Shaun M. ^{[1
,2
,3
]}

Richmond, Rebecca C. ^{[11
,28
]}

Spiegelhalder, Kai ^{[29
]}

Tyrrell, Jessica ^{[6
]}

Zhu, Xiaofeng ^{[30
]}

Hublin, Christer ^{[19
,31
]}

Kaprio, Jaakko A. ^{[19
,31
]}

Kristiansson, Kati ^{[15
]}

Sulkava, Sonja ^{[15
,16
,17
,18
]}

Paunio, Tiina ^{[15
,16
,17
,18
]}

Hveem, Kristian ^{[10
,11
]}

Nielsen, Jonas B. ^{[32
]}

Willer, Cristen J. ^{[32
]}

Zwart, John-Anker ^{[13
,14
]}

Strand, Linn B. ^{[10
]}

Frayling, Timothy M. ^{[6
]}

Ray, David ^{[33
]}

Lawlor, Deborah A. ^{[11
,24
]}

Rutter, Martin K. ^{[23
,34
]}

Weedon, Michael N. ^{[6
]}

Redline, Susan ^{[1
,2
,3
,35
]}

Saxena, Richa ^{[1
,2
,3
,4
,5
]}

机构：

[1] Brigham & Womens Hosp, Div Sleep & Circadian Disorders, 75 Francis St, Boston, MA 02115 USA

[2] Harvard Med Sch, Boston, MA 02115 USA

[3] Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA

[4] Massachusetts Gen Hosp, Ctr Genom Med, Boston, MA 02114 USA

[5] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA

[6] Univ Exeter, Med Sch, Genet Complex Traits, Exeter, Devon, England

[7] Stanford Univ, Dept Psychiat & Behav Sci, Palo Alto, CA 94304 USA

[8] Univ Helsinki, Inst Mol Med Finland, Helsinki, Finland

[9] Netherlands eSci Ctr, Amsterdam, Netherlands

[10] Norwegian Univ Sci & Technol, KG Jebsen Ctr Genet Epidemiol, Dept Publ Hlth & Nursing, Trondheim, Norway

[11] Univ Bristol, MRC, Integrat Epidemiol Unit, Bristol, Avon, England

[12] Trondheim Reg & Univ Hosp, St Olavs Hosp, Dept Thorac & Occupat Med, Trondheim, Norway

[13] Oslo Univ Hosp, Div Clin Neurosci, Oslo, Norway

[14] Univ Oslo, Oslo, Norway

[15] Natl Inst Hlth & Welf, Genom & Biomarkers Unit, Helsinki, Finland

[16] Univ Helsinki, Fac Med, Dept Psychiat, Helsinki, Finland

[17] Univ Helsinki, Fac Med, SleepWell Res Program, Helsinki, Finland

[18] Helsinki Univ Cent Hosp, Helsinki, Finland

[19] Univ Helsinki, HiLIFE, Inst Mol Med FIMM, Helsinki, Finland

[20] Northeastern Univ, Coll Sci, Boston, MA 02115 USA

[21] Univ Manchester, Fac Biol Med & Hlth, Sch Med Sci, Div Cardiovasc Sci, Manchester, Lancs, England

[22] Univ West Indies, Caribbean Inst Hlth Res, George Alleyne Chron Dis Res Ctr, Cave Hill, Wanstead, Barbados

[23] Univ Manchester, Fac Biol Med & Hlth, Sch Med Sci, Div Endocrinol Diabet & Gastroenterol, Manchester, Lancs, England

[24] Univ Bristol, Bristol Med Sch, Populat Hlth Sci, Bristol, Avon, England

[25] Univ Oxford, Sleep & Circadian Neurosci Inst, Nuffield Dept Clin Neurosci, Oxford, England

[26] Aston Univ, Dept Math, Birmingham, W Midlands, England

[27] MIT, Media Lab, Cambridge, MA 02139 USA

[28] Univ Bristol, Sch Social & Community Med, Bristol, Avon, England

[29] Univ Freiburg, Med Ctr, Clin Psychiat & Psychotherapy, Freiburg, Germany

[30] Case Western Reserve Univ, Dept Populat & Quantitat Hlth Sci, Cleveland, OH 44106 USA

[31] Univ Helsinki, Dept Publ Hlth, Helsinki, Finland

[32] Univ Michigan, Dept Internal Med, Div Cardiol, Ann Arbor, MI 48109 USA

[33] John Radcliffe Hosp, NIHR Oxford Biomed Res Ctr, Oxford OX3 9DU, England

[34] Manchester Univ NHS Fdn Trust, Manchester Acad Hlth Sci Ctr, Manchester Diabet Ctr, Manchester, Lancs, England

[35] Beth Israel Deaconess Med Ctr, Dept Sleep Med, Boston, MA 02215 USA

来源：

NATURE COMMUNICATIONS | 2019年 / 10卷 / 1期

基金：

芬兰科学院; 英国医学研究理事会; 英国惠康基金;

关键词：

RESTLESS LEGS; GENETIC INFLUENCES; OBESITY; HERITABILITY; WAKEFULNESS; DISEASE; APNEA; RISK; DISTURBANCE; IMPAIRMENT;

D O I：

10.1038/s41467-019-11456-7

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：12

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