Genetic determinants of daytime napping and effects on cardiometabolic health

被引：152
作者：
Dashti, Hassan S. [1 ,2 ,3 ,4 ]
Daghlas, Iyas [1 ,2 ,3 ]
Lane, Jacqueline M. [1 ,2 ,3 ,4 ]
Huang, Yunru [5 ]
Udler, Miriam S. [1 ,2 ,3 ,6 ,7 ]
Wang, Heming [2 ,3 ,8 ]
Ollila, Hanna M. [1 ,2 ,3 ,9 ,10 ]
Jones, Samuel E. [9 ,11 ]
Kim, Jaegil [12 ]
Weedon, Michael N. [11 ]
Wood, Andrew R. [11 ]
Aslibekyan, Stella [5 ]
Garaulet, Marta [2 ,8 ,13 ,14 ]
Saxena, Richa [1 ,2 ,3 ,4 ]
机构：
[1] Massachusetts Gen Hosp, Ctr Genom Med, Boston, MA 02114 USA
[2] Harvard Med Sch, Boston, MA 02115 USA
[3] Broad Inst, Cambridge, MA 02142 USA
[4] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA
[5] 23AndMe Inc, Sunnyvale, CA USA
[6] Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA
[7] Harvard Med Sch, Dept Med, Boston, MA USA
[8] Brigham & Womens Hosp, Div Sleep & Circadian Disorders, 75 Francis St, Boston, MA 02115 USA
[9] Univ Helsinki, Inst Mol Med FIMM, HiLIFE, Helsinki, Finland
[10] Stanford Univ, Dept Psychiat & Behav Sci, Stanford, CA USA
[11] Univ Exeter, Med Sch, Genet Complex Traits, Exeter, Devon, England
[12] GlaxoSmithKline, Waltham, MA USA
[13] Univ Murcia, Dept Physiol, Murcia, Spain
[14] IMIB Arrixaca, Murcia, Spain
来源：
NATURE COMMUNICATIONS | 2021年 / 12卷 / 01期
基金：
芬兰科学院; 英国医学研究理事会;
关键词：
D O I：
10.1038/s41467-020-20585-3
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：
Daytime napping is a common, heritable behavior, but its genetic basis and causal relationship with cardiometabolic health remain unclear. Here, we perform a genome-wide association study of self-reported daytime napping in the UK Biobank (n=452,633) and identify 123 loci of which 61 replicate in the 23andMe research cohort (n=541,333). Findings include missense variants in established drug targets for sleep disorders (HCRTR1, HCRTR2), genes with roles in arousal (TRPC6, PNOC), and genes suggesting an obesity-hypersomnolence pathway (PNOC, PATJ). Association signals are concordant with accelerometer-measured daytime inactivity duration and 33 loci colocalize with loci for other sleep phenotypes. Cluster analysis identifies three distinct clusters of nap-promoting mechanisms with heterogeneous associations with cardiometabolic outcomes. Mendelian randomization shows potential causal links between more frequent daytime napping and higher blood pressure and waist circumference. The genetic basis of daytime napping and the directional effect of daytime napping on cardiometabolic health are unknown. Here, the authors perform a genome-wide association study on self-reported daytime napping in the UK Biobank and Mendelian randomization to explore causal associations.
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页数：15
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共 105 条
[21]  
Chung F., Et al., STOP questionnaire: a tool to screen patients for obstructive sleep apnea, Anesthesiology, 108, pp. 812-821, (2008)
[22]  
Isaac R.E., Li C., Leedale A.E., Shirras A.D., Drosophila male sex peptide inhibits siesta sleep and promotes locomotor activity in the post-mated female, Proceedings Biol. Sci., 277, pp. 65-70, (2010)
[23]  
Jones S.E., Et al., Genome-wide association analyses of chronotype in 697,828 individuals provides insights into circadian rhythms, Nat. Commun., 10, (2019)
[24]  
Wang H., Et al., Genome-wide association analysis of self-reported daytime sleepiness identifies 42 loci that suggest biological subtypes, Nat. Commun., 10, (2019)
[25]  
Lane J.M., Et al., Biological and clinical insights from genetics of insomnia symptoms, Nat. Genet., 51, pp. 387-393, (2019)
[26]  
Dashti H.S., Et al., Genome-wide association study identifies genetic loci for self-reported habitual sleep duration supported by accelerometer-derived estimates, Nat. Commun., 10, (2019)
[27]  
Bulik-Sullivan B.K., Et al., LD Score regression distinguishes confounding from polygenicity in genome-wide association studies, Nat. Genet., 47, pp. 291-295, (2015)
[28]  
Foley C.N., Et al., A fast and efficient colocalization algorithm for identifying shared genetic risk factors across multiple traits, bioRxiv, 44, (2019)
[29]  
Cvetkovic-Lopes V., Et al., Rat hypocretin/orexin neurons are maintained in a depolarized state by TRPC channels, PLoS ONE, 5, (2010)
[30]  
Chiu C.N., Et al., A zebrafish genetic screen identifies neuromedin U as a regulator of sleep/wake states, Neuron, 89, pp. 842-856, (2016)
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