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

被引:148
|
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
基金
瑞士国家科学基金会; 欧洲研究理事会; 英国医学研究理事会; 英国惠康基金;
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.
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页数:12
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