Do genes matter in sleep?-A comprehensive update

Main Article Content

Rajib Dutta

Abstract

Sleep is considered as a complex process in human beings and is least understood mechanism. Role of sleep in synaptic plasticity remains a debatable topic till date. Sleep is influenced by genetic background of the individual. EEG done in human sleep showed strong influence of genetic factors. A handful of familial analyses involving specific gene loci and twin studies has been done in this regard. In this review article focused discussion on genetic contribution to sleep phenotypes, twin and familial linkage studies and effect of genetic variation on sleep will be covered.

Article Details

Dutta, R. (2020). Do genes matter in sleep?-A comprehensive update. Journal of Neuroscience and Neurological Disorders, 4(1), 014–023. https://doi.org/10.29328/journal.jnnd.1001029
Review Articles

Copyright (c) 2020 Dutta R

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

Veatch OJ, Malow BA. Review of the Genetic Basis of Sleep and Sleep Disorders. JAMA Neurol. 2014; 71: 1058-1060.

Van Beijsterveldt CEM, Molenaar PCM, deGeus EJC, Boomsma DI. Heritability of human brain functioning as assessed by electroencephalography. Am J Hum Genet. 1996; 58: 562-573. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/8644716

Landolt HP. Genetic determination of sleep EEG profiles in healthy humans. Prog Brain Res. 2011; 193: 51-61. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/21854955

Ambrosius U, Lietzenmaier S, Wehrle R, Wichniak A, Kalus S, et al. Heritability of sleep electroencephalogram. Biol Psychiatry. 2008; 64: 344-348. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/18405882

De Gennaro L, Marzano C, Fratello F, Moroni F, Pellicciari MC, et al. The electroencephalographic fingerprint of sleep is genetically determined: a twin study. Ann Neurol. 2008; 64: 455-460. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/18688819

Tafti M, Petit B, Chollet D, Neidhart E ,de Bilbao F, et al. Deficiency in short-chain fatty acid beta-oxidation affects theta oscillations during sleep. Nat Genet. 2003; 34: 320-325. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/12796782

Maret S, Franken P, Dauvilliers Y, Ghyselinck NB, Chambon P, et al. Retinoic acid signaling affects cortical synchrony during sleep. Science. 2005; 310: 111-113. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/16210540

Ashbrook LH, Krystal AD, Fu YH, Ptáček LJ. Genetics of the human circadian clock and sleep homeostat. Neuropsychopharmacology. 2020; 45: 45-54. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/31400754

Frank MG. The mystery of sleep function: current perspectives and future directions. Rev Neurosci. 2006; 17: 375-392. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/17139839

Mignot E. Why we sleep: the temporal organization of recovery. PLoS Biol. 2008; 6: e106. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/18447584

Crocker A, Sehgal A. Genetic analysis of sleep. Genes Dev. 2010; 24: 1220-1235.

Cirelli C. The genetic and molecular regulation of sleep: from fruit flies to humans. Nat Rev Neurosci. 2009; 10: 549-560. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/19617891

Andretic R, Franken P, Tafti M. Genetics of sleep. Annu Rev Genet. 2008; 42: 361-388. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/18983259

Allada R, Siegel JM. Unearthing the phylogenetic roots of sleep. Curr Biol. 2008; 18: R670-R679. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/18682212

Partinen M, Kaprio J, Koskenvuo M. Genetic and environmental determination of human sleep. Sleep. 1983; 6: 179-185. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/6684786

Gedda L, Brenci G. Twins living apart test: progress report. Acta Genet Med Gemellol (Roma). 1983; 32: 17-22. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/6684862

Gedda L, Brenci G. Sleep and dream characteristics in twins. Acta Genet Med Gemellol (Roma). 1979; 28: 237-239. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/575840

Barclay NL, Eley TC, Buysse DJ. Diurnal preference and sleep quality: same genes? A study of young adult twins. Chronobiol Int. 2010; 27: 278-296. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/20370470

Hublin C, Partinen M, Koskenvuo M, Kaprio J. Heritability and mortality risk of insomnia- related symptoms: a genetic epidemiologic study in a population- based twin cohort. Sleep. 2011; 34: 957-964. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/21731146

Rao WW, Li W, Qi H. Sleep quality in medical students: a comprehensive meta-analysis of observational studies. Sleep Breath. 2020; 10. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/32072469

Zung WW, Wilson WP. Sleep and dream patterns in twins. Markov analysis of a genetic trait. Recent Adv Biol Psychiatry. 1966; 9: 119-130. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/4300786

Linkowski P, Kerkhofs M, Hauspie R. Genetic determinants of EEG sleep: a study in twins living apart. Electroencephalogr Clin Neurophysiol. 1991; 79: 114-118. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/1713824

Linkowski P, Kerkhofs M, Hauspie R. EEG sleep patterns in mana twin study. Electroencephalogr Clin Neurophysiol. 1989; 73: 279-284. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/2477214

Kuna ST, Maislin G, Pack FM. Heritability of performance deficit accumulation during acute sleep deprivation in twins. Sleep. 2012; 35: 12231233. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/22942500

Barclay NL, Gregory AM. Quantitative genetic research on sleep: a review of normal sleep, sleep disturbances and associated emotional, behavioural, and health- related difficulties. Sleep Med Rev. 2013; 17: 29-40. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/22560641

Linkowski P. EEG sleep patterns in twins. J Sleep Res. 1999; 8: 11-13.

Tafti M, Franken P, Kitahama K. Localization of candidate genomic regions influencing paradoxical sleep in mice. Neuroreport. 1997; 8: 3755-3758. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/9427364

Franken P., Chollet D, Tafti M. The homeostatic regulation of sleep need is under genetic control. J Neurosci. 2001; 21: 2610-2621. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/11306614

Webb WB, Campbell SS. Relationships in sleep characteristics of identical and fraternal twins. Arch Gen Psychiatry. 1983; 40: 1093-1095. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/6684906

Boomsma DI, Van Someren EJ, Beem AL. Sleep during a regular week night: a twin- sibling study. Twin Res Hum Genet. 2008; 11: 538-545. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/18828737

De Gennaro L, Ferrara M, Vecchio F. An electroencephalographic fingerprint of human sleep. Neuroimage. 2005; 26: 114-122. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/15862211

Hur YM. Stability of genetic influence on morningness- eveningness: a cross- sectional examination of South Korean twins from preadolescence to young adulthood. J Sleep Res. 2007; 16: 17-23. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/17309759

Koskenvuo M, Hublin C, Partinen M. Heritability of diurnal type: a nationwide study of 8753 adult twin pairs. J Sleep Res. 2007; 16: 156-162. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/17542945

Drake CL, Friedman NP, Wright KP Jr, Roth T. Sleep reactivity and insomnia: genetic and environmental influences. Sleep. 2011; 34: 1179-1188. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/21886355

Watson NF, Goldberg J, Arguelles L, Buchwald D. Genetic and environmental influences on insomnia, daytime sleepiness, and obesity in twins. Sleep. 2006; 29: 645-649. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/16774154

Xiong L, Jang K, Montplaisir J. Canadian restless legs syndrome twin study. Neurology. 2007; 68: 1631-1633. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/17485653

Desai AV, Cherkas LF, Spector TD, Williams AJ. Genetic influences in self- reported symptoms of obstructive sleep apnoea and restless legs: a twin study. Twin Res. 2004; 7: 589-595. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/15607009

Hublin C, Kaprio J, Partinen M, Koskenvuo M. Sleep talking in twins: epidemiology and psychiatric comorbidity. Behav Genet. 1998; 28: 289-298.

Hublin C, Kaprio J, Partinen M, Koskenvuo M. Sleep bruxism based on self- report in a nationwide twin cohort. J Sleep Res. 1998; 7: 61-67. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/9613429

Hublin C, Kaprio J, Partinen M, Koskenvuo M. Nocturnal enuresis in a nationwide twin cohort. Sleep. 1998; 21: 579-585. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/9779517

Toh KL, Jones CR, He Y. An hPer2 phosphorylation site mutation in familial advanced sleep phase syndrome. Science. 2001; 291: 1040-1043. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/11232563

Xu Y, Padiath QS, Shapiro RE. Functional consequences of a CKIδ mutation causing familial advanced sleep phase syndrome. Nature. 2005; 434: 640-644. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/15800623

Reid KJ, Chang AM, Dubocovich ML, Turek FW, Takahashi JS, et al. Familial advanced sleep phase syndrome. Arch Neurol. 2001; 58: 1089-1094. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/11448298

Jones CR, Campbell SS, Zone SE. Familial advanced sleep-phase syndrome: A short-period circadian rhythm variant in humans. Nat Med. 1999; 5: 1062-1065. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/10470086

Satoh K, Mishima K, Inoue Y, Ebisawa T, Shimizu T. Two pedigrees of familial advanced sleep phase syndrome in Japan. Sleep. 2003; 26: 416-417. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/12841366

Vanselow K, Vanselow JT, Westermark PO. Differential effects of PER2 phosphorylation: molecular basis for the human familial advanced sleep phase syndrome (FASPS). Genes Dev. 2006; 20: 2660-2672. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/16983144

Chen P, Ijomone OM, Lee KH, Aschner M. Caenorhabditis elegans and its applicability to studies on restless legs syndrome. Adv Pharmacol. 2019; 84: 14-174. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/31229169

Chen S, Ondo WG, Rao S. Genomewide linkage scan identifies a novel susceptibility locus for restless legs syndrome on chromosome 9p. Am J Hum Genet 2004; 74: 876-885. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/15077200

Vogl FD, Pichler I, Adel S. Restless legs syndrome: epidemiological and clinicogenetic study in a South Tyrolean population isolate. Mov Disord. 2006; 21: 1189-1195. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/16685686

Caylak E. The genetics of sleep disorders in humans: narcolepsy, restless legs syndrome, and obstructive sleep apnea syndrome. Am J Med Genet A. 2009; 149: 2612-2626. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/19876894

Winkelmann J, Muller MB. Genetics of restless legs syndrome: a burning urge to move. Neurology. 2008; 70: 664-645. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/18299518

Winkelmann J, Polo O, Provini F. Genetics of restless legs syndrome (RLS): State-of-the-art and future directions. Mov Disord. 2007; 22: S449-S458. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/17557342

Lohmann HK, Neumann A, Kleensang A. Evidence for linkage of restless legs syndrome to chromosome 9p: are there two distinct loci? Neurology. 2008; 70: 686-694. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/18032746

Levchenko A, Provost S, Montplaisir JY. A novel autosomal dominant restless legs syndrome locus maps to chromosome 20p13. Neurology. 2006; 67: 900-901. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/16966564

Pichler I, Marroni F, Volpato CB. Linkage analysis identifies a novel locus for restless legs syndrome on chromosome 2q in a South Tyrolean population isolate. Am J Hum Genet. 2006; 79: 716-723. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/16960808

Desautels A, Turecki G, Montplaisir J. Identification of a major susceptibility locus for restless legs syndrome on chromosome 12q. Am J Hum Genet. 2001; 69: 1266-1270. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/11704926

Bonati MT, Ferini SL, Aridon P. Autosomal dominant restless legs syndrome maps on chromosome 14q. Brain. 2003; 126: 1485-1492. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/12764067

Kock N, Culjkovic B, Maniak S. Mode of inheritance and susceptibility locus for restless legs syndrome, on chromosome 12q. Am J Hum Genet. 2002; 71: 205-208. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/12068378

Liebetanz KM, Winkelmann J, Trenkwalder C. RLS3: fine-mapping of an autosomal dominant locus in a family with intrafamilial heterogeneity. Neurology. 2006; 67: 320-321. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/16864828

Desautels A, Turecki G, Montplaisir J. Restless legs syndrome:confirmation of linkage to chromosome 12q, genetic heterogeneity, and evidence of complexity. Arch Neurol. 2005; 62: 591-596. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/15824258

Sarayloo F, Dionne LA, Catoire H. Mineral absorption is an enriched pathway in a brain region of restless legs syndrome patients with reduced MEIS1 expression. PLoS One. 2019; 14: e0225186. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/31725784

Sarayloo F, Dion PA, Rouleau GA. MEIS1 and Restless Legs Syndrome: A Comprehensive Review. Front Neurol. 2019; 10: 935. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/31551905

Salminen AV, Lam DD, Winkelmann J. Role of MEIS1 in restless legs syndrome: From GWAS to functional studies in mice. Adv Pharmacol. 2019; 84: 175-184. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/31229170

Levchenko A, Montplaisir JY, Dube MP. The 14q restless legs syndrome locus in the French Canadian population. Ann Neurol. 2004; 55: 887-891. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/15174026

Winkelmann J, Lichtner P, Putz B. Evidence for further genetic locus heterogeneity and confirmation of RLS-1 in restless legs syndrome. Mov Disord. 2006; 21: 28-33. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/16124010

Winkelmann J, Schormair B, Lichtner P. Genome- wide association study of restless legs syndrome identifies common variants in three genomic regions .Nat Genet. 2007; 39: 1000-1006. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/17637780

Xiong L, Dion P, Montplaisir J. Molecular genetic studies of DMT1 on 12q in French-Canadian restless legs syndrome patients and families. Am J Med Genet B Neuropsychiatr Genet. 2007; 144: 911-917. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/17510944

Stefansson H, Rye DB, Hicks A. A genetic risk factor for periodic limb movements in sleep. N Engl J Med. 2007; 357: 639-647. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/17634447

Tilch E, Schormair B, Zhao C. Identification of Restless Legs Syndrome Genes by Mutational Load Analysis. Ann Neurol. 2020; 87: 184-193. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/31788832

Karroum EG, Saini PS, Trotti LM, Rye DB. TOX3 gene variant could be associated with painful restless legs. Sleep Med. 2020; 65: 4-7. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/31706190

Eiberg H, Berendt I, Mohr J. Assignment of dominant inherited nocturnal enuresis (ENUR1) to chromosome 13q. Nat Genet. 1995; 10: 354-356. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/7670476

Eiberg H, Shaumburg HL, Von Gontard A, Rittig S. Linkage study of a large Danish 4- generation family with urge incontinence and nocturnal enuresis. J Urol. 2001; 166: 2401-2403. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/11696797

Von GA, Eiberg H, Hollmann E. Molecular genetics of nocturnal enuresis: clinical and genetic heterogeneity. Acta Paediatr. 1998; 87: 571-578. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/9641742

Arnell H, Hjalmas K, Jagervall M. The genetics of primary nocturnal enuresis: inheritance and suggestion of a second major gene on chromosome 12q. J Med Genet. 1997; 34: 360-365. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/9152831

Deen PM, Dahl N, Caplan MJ. The aquaporin- 2 water channel in autosomal dominant primary nocturnal enuresis. J Urol. 2002; 167: 1447-1450. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/11832768

Eiberg H. Total genome scan analysis in a single extended family for primary nocturnal enuresis: evidence for a new locus (ENUR3) for primary nocturnal enuresis on chromosome 22q11. Eur Urol. 1998; 33: 34-36. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/9599735

Ece A, Coşkun S, Şahin C, Tan I, Karabel D, et al. BDNF and NGF gene polymorphisms and urine BDNF-NGF levels in children with primary monosymptomatic nocturnal enuresis. J Pediatr Urol. 2019; 15: 255.e1-255.e7. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/30981636

Yu B, Chang N, Lu Y, Ma H, Liu N, et al. Effect of DRD4 receptor -616 C/G polymorphism on brain structure and functional connectivity density in pediatric primary nocturnal enuresis patients. Sci Rep. 2017; 7: 1226. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/28450726

Dai XM, Ma HW, Lu Y, Pan XX. Relationship between dopamine D4 receptor gene polymorphisms and primary nocturnal enuresis. Zhongguo Dang Dai Er Ke Za Zhi. 2008; 10: 607-610. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/18947481

Fatouh AA, Motawie AA, Abd Al-Aziz AM. Anti-diuretic hormone and genetic study in primary nocturnal enuresis. J Pediatr Urol. 2013; 9: 831-837. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/23246575

Wei CC, Wan L, Lin WY, Tsai FJ. Rs 6313 polymorphism in 5-hydroxytryptamine receptor 2A gene association with polysymptomatic primary nocturnal enuresis. J Clin Lab Anal. 2010; 24: 371-375. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/21089166

Wisor JP, O’Hara BF, Terao A. A role for cryptochromes in sleep regulation. BMC Neurosci. 2002; 3: 20. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/12495442

Franken P, Dudley CA, Estill SJ. NPAS2 as a transcriptional regulator of non- rapid eye movement sleep: genotype and sex interactions. Proc Natl Acad Sci USA. 2006; 103: 7118-7123. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/16636276

Laposky A, Easton A, Dugovic C. Deletion of the mammalian circadian clock gene BMAL1/ Mop3 alters baseline sleep architecture and the response to sleep deprivation. Sleep. 2005; 28: 395-409. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/16171284

Katzenberg D, Young T, Finn L. A CLOCK polymorphism associated with human diurnal preference. Sleep. 1998; 21: 569-576. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/9779516

Mishima K, Tozawa T, Satoh K. The 3111T/C polymorphism of hClock is associated with evening preference and delayed sleep timing in a Japanese population sample. Am J Med Genet B Neuropsychiatr Genet. 2005; 133B: 101-104. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/15578592

Morris AR, Stanton DL, Roman D, Liu AC. Systems Level Understanding of Circadian Integration with Cell Physiology. J Mol Biol. 2020. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/32061938

Hor CN, Yeung J, Jan M, et al. Sleep-wake-driven and circadian contributions to daily rhythms in gene expression and chromatin accessibility in the murine cortex. Proc Natl Acad Sci USA. 2019; 116: 25773-25783. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/31776259

Charrier A, Olliac B, Roubertoux P, Tordjman S. Clock Genes and Altered Sleep-Wake Rhythms: Their Role in the Development of Psychiatric Disorders. Int J Mol Sci. 2017; 18: 938. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/28468274

Von Schantz M, Archer SN. Clocks, genes and sleep. J R Soc Med. 2003; 96: 486-489. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/14519724

Landgraf D, Shostak A, Oster H. Clock genes and sleep. Pflugers Arch. 2012; 463: 3-14. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/21833490

Comasco E, Nordquist N, Göktürk C. The clock gene PER2 and sleep problems: association with alcohol consumption among Swedish adolescents. Ups J Med Sci. 2010; 115: 41-48. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/20187847

Archer. Inter-Individual Differences In Habitual Sleep Timing and Entrained Phase of Endogenous Circadian Rhythms of BMAL1, PER2 and PER3 mRNA in Human Leukocytes. Sleep. 2008; 31: 608-617. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/18517031

Holst SC, Bersagliere A, Bachmann V. Dopaminergic role in regulating neurophysiological markers of sleep homeostasis in humans. J Neurosci. 2014; 34: 566-573. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/24403155

Rhodes JA, Lane JM, Vlasac IM, Rutter MK, Czeisler CA, et al. Association of DAT1 genetic variants with habitual sleep duration in the UK Biobank. Sleep. 2019; 42: zsy193. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/30299516

Satterfield BC, Wisor JP, Schmidt MA, Van Dongen HPA. Time-on-Task Effect During Sleep Deprivation in Healthy Young Adults Is Modulated by Dopamine Transporter Genotype. Sleep. 2017; 40: zsx167. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/29029252

Holst SC, Müller T, Valomon A, Seebauer B, Berger W, et al. Functional Polymorphisms in Dopaminergic Genes Modulate Neurobehavioral and Neurophysiological Consequences of Sleep Deprivation. Sci Rep. 2017; 7: 45982. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/28393838

Costa A, Riedel M, Muller U. Relationship between SLC6A3 genotype and striatal dopamine transporter availability: a meta- analysis of human single photon emission computed tomography studies. Synapse. 2011; 65: 998-1005. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/21404331

Dauvilliers Y, Neidhart E, Lecendreux M. MAO- A and COMT polymorphisms and gene effects in narcolepsy. Mol Psychiatry. 2001; 6: 367-372. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/11443519

Brummett BH, Krystal AD, Siegler IC. Associations of a regulatory polymorphism of monoamine oxidase- A gene promoter (MAOA- uVNTR) with symptoms of depression and sleep quality. Psychosom Med. 2007; 69: 396-401. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/17585061

Desautels A, Turecki G, Montplaisir J. Evidence for a genetic association between monoamine oxidase A and restless legs syndrome. Neurology. 2002; 59: 215-219. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/12136060

Koch H, Craig I, Dahlitz M. Analysis of the monoamine oxidase genes and the Norrie disease gene locus in narcolepsy. Lancet. 1999; 353: 645-646. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/10030338

Kozochkin DA, Manukhina EB, Downey HF. The role of microsomal oxidation in the regulation of monoamine oxidase activity in the brain and liver of rats. Gen Physiol Biophys. 2017; 36: 455-464. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/28653655

Wang Z, Chen L, Zhang L, Wang X. Paradoxical sleep deprivation modulates depressive-like behaviors by regulating the MAOA levels in the amygdala and hippocampus. Brain Res. 2017; 1664: 17-24. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/28365314

Ozen F, Yegin Z, Yavlal F, Saglam ZA, Koc H, et al. Lack of association between MAOA-uVNTR variants and excessive daytime sleepiness. Neurol Sci. 2017; 38: 769-774. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/28181067

Joëlle A. Sleep and waking in mutant mice that do not express various proteins involved in serotonergic neurotransmission such as the serotonergic transporter, monoamine oxidase A, and 5-HT1A, 5-HT1B, 5-HT2A, 5-HT2C and 5-HT7 receptors Serotonin and Sleep. Molecular, Functional and Clinical Aspects. 2008.

Retey JV, Adam M, Honegger E. A functional genetic variation of adenosine deaminase affects the duration and intensity of deep sleep in humans. Proc Natl Acad Sci USA. 2005; 102: 15676-15681. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/16221767

Bachmann V, Klaus F, Bodenmann S. Functional ADA polymorphism increases sleep depth and reduces vigilant attention in humans. Cereb Cortex. 2012; 22: 962-970. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/21734253

Radulovacki M. Role of adenosine in sleep in rats. Rev Clin Basic Pharm. 1985; 5: 327-339. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/3916307

Porkka-Heiskanen T. Adenosine in sleep and wakefulness. Ann Med. 1999; 31: 125-129. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/10344585

Mazzotti DR, Guindalini C, de Souza AA. Adenosine deaminase polymorphism affects sleep EEG spectral power in a large epidemiological sample. PLoS One. 2012; 7: e44154. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/22952909

Mackiewicz M, Nikonova EV, Bell CC. Activity of adenosine deaminase in the sleep regulatory areas of the rat CNS. Brain Res Mol Brain Res. 2000; 80: 252-255. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/11038259

Bachmann V, Klein C, Bodenmann S. The BDNF Val66Met polymorphism modulates sleep intensity: EEG frequency- and state-specificity. Sleep. 2012; 35: 335-344. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/22379239

Furihata R, Saitoh K, Otsuki R. Association between reduced serum BDNF levels and insomnia with short sleep duration among female hospital nurses. Sleep Med. 2019; 68: 167-172. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/32044553

Flores KR, Viccaro F, Aquilini M. Protective role of brain derived neurotrophic factor (BDNF) in obstructive sleep apnea syndrome (OSAS) patients. PLoS One. 2020; 15: e0227834. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/31951637

Rahmani M, Rahmani F, Rezaei N. The Brain-Derived Neurotrophic Factor: Missing Link between Sleep Deprivation, Insomnia, and Depression. Neurochem Res. 2020; 45: 221-231. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/31782101

Cullen T, Thomas G, Wadley AJ. Sleep Deprivation: Cytokine and Neuroendocrine Effects on Perception of Effort. Med Sci Sports Exerc. 2019. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/31764462

Tchekalarova J, Kortenska L, Ivanova N, Atanasova M, Marinov P. Agomelatine treatment corrects impaired sleep-wake cycle and sleep architecture and increases MT1 receptor as well as BDNF expression in the hippocampus during the subjective light phase of rats exposed to chronic constant light. Psychopharmacology (Berl). 2020; 237: 503-518. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/31720718

Sun W, Li J, Cui S, Luo L, Huang P, et al. Sleep Deprivation Disrupts Acquisition of Contextual Fear Extinction by Affecting Circadian Oscillation of Hippocampal-Infralimbic proBDNF. eNeuro. 2019; 6: 0165-0219. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/31585927

Mahboubi S, Nasehi M, Imani A, Sadat-Shirazi MS, Zarrindast MR, et al. Benefit effect of REM-sleep deprivation on memory impairment induced by intensive exercise in male wistar rats: with respect to hippocampal BDNF and TrkB. Nat Sci Sleep. 2019; 11: 179-188. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/31576186

Sweeten BLW, Sutton AM, Wellman LL, Sanford LD. Predicting stress resilience and vulnerability: brain-derived neurotrophic factor and rapid eye movement sleep as potential biomarkers of individual stress responses. Sleep. 2020; 43: 199. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/31556950

R Staats. Regulation of brain-derived neurotrophic factor (BDNF) during sleep apnoea treatment. Thorax. 2005; 60: 688-692. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/16061712

Karen S, Edith HT, Anne E. BDNF in sleep, insomnia, and sleep deprivation. Annals of Medicine. 2016; 48: 42-51. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/26758201

Duncan WC, Sarasso S, Ferrarelli F. Concomitant BDNF and sleep slow wave changes indicate ketamine-induced plasticity in major depressive disorder. Int J Neuropsychopharmacol. 2013; 16: 301-311. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/22676966

Medori R, Montagna P, Tritschler HJ, LeBlanc A, Cortelli P, et al. Fatal familial insomnia: a second kindred with mutation of prion protein gene at codon 178. Neurology. 1992; 42: 669-670. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/1347910

Monari L, Chen SG, Brown P, Parchi P, Petersen RB, et al. Fatal familial insomnia and familial Creutzfeldt– Jakob disease: different prion proteins determined by a DNA polymorphism. Proc Natl Acad Sci U S A. 1994; 91: 2839-2842. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/7908444

da Luz MHM, Pino JMV, Santos TG, Antunes HKM, Martins VR, et al. Sleep deprivation regulates availability of PrPC and Aβ peptides which can impair interaction between PrPC and laminin and neuronal plasticity. J Neurochem. 2020; e14960. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/31950499

He R, Hu Y, Yao L, Tian Y, Zhou Y, et al. Clinical features and genetic characteristics of two Chinese pedigrees with fatal family insomnia. Prion. 2019; 13: 116-123. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/31122137

Abu-Rumeileh S, Redaelli V, Baiardi S, Mackenzie G, Windl O, et al. Sporadic Fatal Insomnia in Europe: Phenotypic Features and Diagnostic Challenges. Ann Neurol. 2018; 84: 347-360. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/30048013

Goldfarb LG, Petersen RB, Tabaton M, Brown P, LeBlanc AC, et al. Fatal familial insomnia and familial Creutzfeldt– Jakob disease: disease phenotype determined by a DNA polymorphism. Science. 1992; 258: 806-808. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/1439789

Bodenmann S, Hohoff C, Freitag C, Deckert J, Rétey JV, et al. Polymorphisms of ADORA2A modulate psychomotor vigilance and the effects of caffeine on neurobehavioural performance and sleep EEG after sleep deprivation. Br J Pharmacol. 2012; 165: 1904-1913. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/21950736

Retey JV, Adam M, Khatami R, Luhmann UF, Jung HH, et al. A genetic variation in the adenosine A2A receptor gene (ADORA2A) contributes to individual sensitivity to caffeine effects on sleep. Clin Pharmacol Ther. 2007; 81: 692-698. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/17329997

Bodenmann S, Xu S, Luhmann UF, Arand M, Berger W, et al. Pharmacogenetics of modafinil after sleep loss: catechol- O- methyltransferase genotype modulates waking functions but not recovery sleep. Clin Pharmacol Ther. 2009; 85: 296-304. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/19037200

Bodenmann S, Landolt HP. Effects of modafinil on the sleep EEG depend on Val158Met genotype of COMT. Sleep. 2010; 33: 1027-1035. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/20815183

Goel N, Banks S, Lin L. Catechol- O- methyltransferase Val158Met polymorphism associates with individual differences in sleep physiologic responses to chronic sleep loss. PLoS One. 2011; 6: e29283. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/22216231

Wieczorek S, Gencik M, Rujescu D, Tonn P, Giegling I, et al. TNFA promoter polymorphisms and narcolepsy. Tissue Antigens. 2003; 61: 437-442. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/12823767

Hohjoh H, Nakayama T, Ohashi J. Significant association of a single nucleotide polymorphism in the tumor necrosis factor- alpha (TNF- alpha) gene promoter with human narcolepsy. Tissue Antigens. 1999; 54: 138-145. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/10488740

Archer SN, Carpen JD, Gibson M, Lim GH, Johnston JD, et al. Polymorphism in the PER3 promoter associates with diurnal preference and delayed sleep phase disorder. Sleep. 2010; 33: 695-701. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/20469812

Archer SN, Robilliard DL, Skene DJ, Smits M, Williams A, et al. A length polymorphism in the circadian clock gene Per3 is linked to delayed sleep phase syndrome and extreme diurnal preference. Sleep. 2003; 26: 413-415. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/12841365

Ebisawa T, Uchiyama M, Kajimura N, Mishima K, Kamei Y, et al. Association of structural polymorphisms in the human period3 gene with delayed sleep phase syndrome. EMBO Rep. 2001; 2: 342-346. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/11306557

Goel N, Banks S, Mignot E, Dinges DF. PER3 polymorphism predicts cumulative sleep homeostatic but not neurobehavioral changes to chronic partial sleep deprivation. PLoS One. 2009; 4: e5874. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/19516903

Groeger JA, Viola AU, Lo JC. Early morning executive functioning during sleep deprivation is compromised by a PERIOD3 polymorphism. Sleep. 2008; 31: 1159-1167. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/18714788

Viola AU, Archer SN, James LM, Groeger JA, Lo JC. PER3 polymorphism predicts sleep structure and waking performance. Curr Biol. 2007; 17: 613-618. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/17346965

Hohjoh H, Terada N, Kawashima M, Honda Y, Tokunaga K. Significant association of the tumor necrosis factor receptor 2 (TNFR2) gene with human narcolepsy. Tissue Antigens. 2000; 56: 446-448. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/11144293

Chen YH, Huang YS, Chen CH. Increased plasma level of tumor necrosis factor α in patients with narcolepsy in Taiwan. Sleep Med. 2013; 14: 1272-1276. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/24157100

Peyron C, Faraco J, Rogers W, Ripley B, Overeem S, et al. A mutation in a case of early onset narcolepsy and a generalized absence of hypocretin peptides in human narcoleptic brains. Nat Med. 2000; 6: 991-997. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/10973318

Latorre D, Kallweit U, Armentani E, Foglierini M1, Mele F, et al. T cells in patients with narcolepsy target self-antigens of hypocretin neurons. Nature. 2018; 562: 63-68. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/30232458

Takenoshita S, Sakai N, Chiba Y, Matsumura M, Yamaguchi M, et al. An overview of hypocretin based therapy in narcolepsy. Expert Opin Investig Drugs. 2018; 27: 389-406. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/29623725

Buhr A, Bianchi MT, Baur R. Functional characterization of the new human GABA A receptor mutation β 3 (R192H). Hum Genet. 2002; 111: 154-160. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/12189488

Wisden W, Yu X, Franks NP. GABA Receptors and the Pharmacology of Sleep. Handb Exp Pharmacol. 2019; 253: 279-304. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/28993837

Toossi H, Del Cid-Pellitero E, Jones BE. GABA Receptors on Orexin and Melanin-Concentrating Hormone Neurons Are Differentially Homeostatically Regulated Following Sleep Deprivation. eNeuro. 2016; 3: 0077-0116. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/27294196

Felsing DE, Anastasio NC, Miszkiel JM, Gilbertson SR, Allen JA, et al. Biophysical validation of serotonin 5-HT2A and 5-HT2C receptor interaction. PLoS One. 2018; 13: e0203137. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/30157263

Gao X, Ge H, Jiang Y, Lian Y, Zhang C, et al. Relationship between Job Stress and 5-HT2A Receptor Polymorphisms on Self-Reported Sleep Quality in Physicians in Urumqi (Xinjiang, China): A Cross-Sectional Study. Int J Environ Res Public Health. 2018; 15: 1034. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/29883419

Zhao Y, Tao L, Nie P, Lu X, Xu X, et al. Association between 5- HT 2A receptor polymorphisms and risk of obstructive sleep apnea and hypopnea syndrome: a systematic review and meta- analysis. Gene. 2013; 530: 287-294. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/23988500

Wu Y, Liu HB, Ding M, Liu JN, Zhu XF, et al. Association between the −1438G/ A and T102C polymorphisms of 5- HT 2A receptor gene and obstructive sleepapnea:a meta- analysis. Mol Biol Rep. 2013; 40: 6223-6231. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/24065538

Van Dalfsen JH, Markus CR. The serotonin transporter gene-linked polymorphic region (5-HTTLPR) and the sleep-promoting effects of tryptophan: A randomized placebo-controlled crossover study. J Psychopharmacol. 2019; 33: 948-954. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/31237183

Barclay NL, Eley TC, Mill J. Sleep quality and diurnal preference in a sample of young adults: associations with 5HTTLPR, PER3, and CLOCK 3111. Am J Med Genet B Neuropsychiatr Genet. 2011; 156: 681-690. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/21714069

Brummett BH, Krystal AD, Ashley-Koch A, Kuhn CM, Züchner S, et al. Sleep quality varies as a function of 5- HTTLPR genotype and stress. Psychosom Med. 2007; 69: 621-624. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/17766685

Carskadon MA, Sharkey KM, Knopik VS, McGeary JE. Short sleep as an environmental exposure: a preliminary study associating 5- HTTLPR genotype to self- reported sleep duration and depressed mood in first-year university students. Sleep. 2012; 35: 791-796. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/22654198

Deuschle M, Schredl M, Schilling C, Wüst S, Frank J, et al. Association between a serotonin transporter length polymorphism and primary insomnia. Sleep. 2010; 33: 343-347. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/20337192