Genetic studies of accelerometer-based sleep measures yield new insights into human sleep behaviour

被引：173

作者：

Jones, Samuel E. ^{[1
]}

van Hees, Vincent T. ^{[2
]}

Mazzotti, Diego R. ^{[3
,4
]}

Marques-Vidal, Pedro ^{[5
]}

Sabia, Severine ^{[6
,7
]}

van der Spek, Ashley ^{[8
]}

Dashti, Hassan S. ^{[9
,10
]}

Engmann, Jorgen ^{[11
]}

Kocevska, Desana ^{[8
,12
]}

Tyrrell, Jessica ^{[1
]}

Beaumont, Robin N. ^{[1
]}

Hillsdon, Melvyn ^{[13
]}

Ruth, Katherine S. ^{[1
]}

Tuke, Marcus A. ^{[1
]}

Yaghootkar, Hanieh ^{[1
]}

Sharp, Seth A. ^{[1
]}

Ji, Yingjie ^{[1
]}

Harrison, Jamie W. ^{[1
]}

Freathy, Rachel M. ^{[1
]}

Murray, Anna ^{[1
]}

Luik, Annemarie I. ^{[8
]}

Amin, Najaf ^{[8
]}

Lane, Jacqueline M. ^{[9
,10
]}

Saxena, Richa ^{[9
,14
,15
,16
,17
]}

Rutter, Martin K. ^{[18
,19
]}

Tiemeier, Henning ^{[8
,20
]}

Kutalik, Zoltan ^{[21
,22
]}

Kumari, Meena ^{[23
]}

Frayling, Timothy M. ^{[1
]}

Weedon, Michael N. ^{[1
]}

Gehrman, Philip R. ^{[3
,4
]}

Wood, Andrew R. ^{[1
]}

机构：

[1] Univ Exeter, Coll Med & Hlth, Genet Complex Traits, Exeter EX2 5DW, Devon, England

[2] Netherlands eSci Ctr, NL-1098 XG Amsterdam, Netherlands

[3] Univ Penn, Ctr Sleep & Circadian Neurobiol, Philadelphia, PA 19104 USA

[4] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA

[5] Lausanne Univ Hosp, Dept Med, Internal Med, CH-1011 Lausanne, Switzerland

[6] UCL, Res Dept Epidemiol & Publ Hlth, London WC1E 6BT, England

[7] Univ Paris, INSERM, U1153, Epidemiol Ageing & Neurodegenerat Dis, F-75010 Paris, France

[8] Erasmus MC Univ Med Ctr, Dept Epidemiol, NL-3000 CA Rotterdam, Netherlands

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

[10] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA

[11] UCL Inst Cardiovasc Sci, Res Dept Populat Sci & Expt Med, Ctr Translat Genom, 222 Euston Rd, London NW1 2DA, England

[12] Erasmus MC, Dept Child & Adolescent Psychiat, NL-3000 CA Rotterdam, Netherlands

[13] Univ Exeter, Coll Life & Environm Sci, Sport & Hlth Sci, Exeter EX1 2LU, Devon, England

[14] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02111 USA

[15] Harvard Med Sch, Boston, MA 02111 USA

[16] Brigham & Womens Hosp, Dept Med, 75 Francis St, Boston, MA 02115 USA

[17] Harvard Med Sch, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA

[18] Univ Manchester, Fac Med Biol & Hlth, Div Diabet Endocrinol & Gastroenterol, Manchester M13 9PL, Lancs, England

[19] Manchester Univ NHS Fdn Trust, Manchester Acad Hlth Sci Ctr, Manchester Diabet Ctr, Oxford Rd,193 Hathersage Rd, Manchester M13 0JE, Lancs, England

[20] Harvard TH Chan Sch Publ Hlth, Dept Social & Behav Sci, Boston, MA 02115 USA

[21] Lausanne Univ Hosp, Inst Social & Prevent Med IUMSP, CH-1010 Lausanne, Switzerland

[22] Swiss Inst Bioinformat, CH-1015 Lausanne, Switzerland

[23] Univ Essex, ISER, Colchester CO4 3SQ, Essex, England

来源：

NATURE COMMUNICATIONS | 2019年 / 10卷 / 1期

基金：

英国医学研究理事会; 英国惠康基金; 欧洲研究理事会; 瑞士国家科学基金会;

关键词：

GENOME-WIDE ASSOCIATION; LD SCORE REGRESSION; ALZHEIMERS-DISEASE; SEDENTARY BEHAVIOR; PHYSICAL-ACTIVITY; RISK LOCI; DURATION; OBESITY; INDIVIDUALS; DISTURBANCE;

D O I：

10.1038/s41467-019-09576-1

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：

Sleep is an essential human function but its regulation is poorly understood. Using accelerometer data from 85,670 UK Biobank participants, we perform a genome-wide association study of 8 derived sleep traits representing sleep quality, quantity and timing, and validate our findings in 5,819 individuals. We identify 47 genetic associations at P < 5 x 10(-8), of which 20 reach a stricter threshold of P < 8 x 10(-10). These include 26 novel associations with measures of sleep quality and 10 with nocturnal sleep duration. The majority of identified variants associate with a single sleep trait, except for variants previously associated with restless legs syndrome. For sleep duration we identify a missense variant (p.Tyr727Cys) in PDE11A as the likely causal variant. As a group, sleep quality loci are enriched for serotonin processing genes. Although accelerometer-derived measures of sleep are imperfect and may be affected by restless legs syndrome, these findings provide new biological insights into sleep compared to previous efforts based on self-report sleep measures.

引用

页数：12

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