Genome-wide association study identifies genetic loci for self-reported habitual sleep duration supported by accelerometer-derived estimates

被引：417

作者：

Dashti, Hassan S. ^{[1
,2
,3
]}

Jones, Samuel E. ^{[4
]}

Wood, Andrew R. ^{[4
]}

Lane, Jacqueline M. ^{[1
,2
,3
,5
]}

van Hees, Vincent T. ^{[6
]}

Wang, Heming ^{[3
,7
,8
]}

Rhodes, Jessica A. ^{[1
,2
,3
]}

Song, Yanwei ^{[1
,2
,9
]}

Patel, Krunal ^{[1
,2
,9
]}

Anderson, Simon G. ^{[10
]}

Beaumont, Robin N. ^{[4
]}

Bechtold, David A. ^{[11
]}

Bowden, Jack ^{[12
,13
]}

Cade, Brian E. ^{[3
,7
,8
]}

Garaulet, Marta ^{[14
,15
]}

Kyle, Simon D. ^{[16
]}

Little, Max A. ^{[17
,18
]}

Loudon, Andrew S. ^{[11
]}

Luik, Annemarie, I ^{[16
]}

Scheer, Frank A. J. L. ^{[3
,8
,19
,20
]}

Spiegelhalder, Kai ^{[21
]}

Tyrrell, Jessica ^{[4
]}

Gottlieb, Daniel J. ^{[7
,8
,22
]}

Tiemeier, Henning ^{[23
,24
]}

Ray, David W. ^{[11
]}

Purcell, Shaun M. ^{[25
]}

Frayling, Timothy M. ^{[4
]}

Redline, Susan ^{[26
,27
]}

Lawlor, Deborah A. ^{[12
,13
]}

Rutter, Martin K. ^{[11
,28
]}

Weedon, Michael N. ^{[4
]}

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

机构：

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

[2] Harvard Med Sch, Boston, MA 02114 USA

[3] Broad Inst, Cambridge, MA 02142 USA

[4] Univ Exeter, Med Sch, Genet Complex Traits, Exeter EX2 5DW, Devon, England

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

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

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

[8] Harvard Med Sch, Div Sleep Med, Boston, MA 02115 USA

[9] Northeastern Univ, Coll Sci, 176 Mugar Life Sci,360 Huntington Ave, Boston, MA 02015 USA

[10] Univ Manchester, Fac Biol Med & Hlth, Sch Med Sci, Div Cardiovasc Sci, Manchester M13 9PL, Lancs, England

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

[12] Univ Bristol, MRC Integrat Epidemiol Unit, Bristol BS8 2BN, Avon, England

[13] Univ Bristol, Bristol Med Sch, Populat Hlth Sci, Bristol BS8 2BN, Avon, England

[14] Univ Murcia, Dept Physiol, E-30100 Murcia, Spain

[15] IMIB Arrixaca, Murcia 30120, Spain

[16] Univ Oxford, Sleep & Circadian Neurosci Inst, Nuffield Dept Clin Neurosci, Oxford OX3 7LF, England

[17] Aston Univ, Dept Math, Birmingham B4 7ET, W Midlands, England

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

[19] Brigham & Womens Hosp, Dept Med, Div Sleep & Circadian Disorders, Med Chronobiol Program, 75 Francis St, Boston, MA 02115 USA

[20] Brigham & Womens Hosp, Dept Neurol, Div Sleep & Circadian Disorders, Med Chronobiol Program, 75 Francis St, Boston, MA 02115 USA

[21] Univ Freiburg, Fac Med, Clin Psychiat & Psychotherapy, Med Ctr, D-79106 Freiburg, Germany

[22] VA Boston Healthcare Syst, Boston, MA 02132 USA

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

[24] Erasmus MC, Dept Epidemiol, NL-3015 Rotterdam, Netherlands

[25] Harvard Med Sch, Brigham & Womens Hosp, Dept Psychiat, Boston, MA 02115 USA

[26] Harvard Med Sch, Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA

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

[28] Manchester Univ NHS Fdn Trust, Manchester Acad Hlth Sci Ctr, Manchester Diabet Ctr, Manchester M13 9PL, Lancs, England

来源：

NATURE COMMUNICATIONS | 2019年 / 10卷 / 1期

基金：

英国惠康基金; 英国医学研究理事会;

关键词：

LD SCORE REGRESSION; BODY-MASS INDEX; MENDELIAN RANDOMIZATION; SCHIZOPHRENIA; HERITABILITY; METAANALYSIS; VARIANTS; DISEASE; RISK; WAKEFULNESS;

D O I：

10.1038/s41467-019-08917-4

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：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

Sleep is an essential state of decreased activity and alertness but molecular factors regulating sleep duration remain unknown. Through genome-wide association analysis in 446,118 adults of European ancestry from the UK Biobank, we identify 78 loci for self-reported habitual sleep duration (p < 5 x 10(-8); 43 loci at p < 6 x 10(-9)). Replication is observed for PAX8, VRK2, and FBXL12/UBL5/PIN1 loci in the CHARGE study (n = 47,180; p < 6.3 x 10(-4)), and 55 signals show sign-concordant effects. The 78 loci further associate with accelerometer-derived sleep duration, daytime inactivity, sleep efficiency and number of sleep bouts in secondary analysis (n = 85,499). Loci are enriched for pathways including striatum and subpallium development, mechanosensory response, dopamine binding, synaptic neurotransmission and plasticity, among others. Genetic correlation indicates shared links with anthropometric, cognitive, metabolic, and psychiatric traits and two-sample Mendelian randomization highlights a bidirectional causal link with schizophrenia. This work provides insights into the genetic basis for inter-individual variation in sleep duration implicating multiple biological pathways.

引用

页数：12

共 73 条

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