title: Genetic and immunologic aspects of sleep and sleep disorders.
abstract: The study of genetics is providing new and exciting insights into the pathogenesis, diagnosis, and treatment of disease. Both normal sleep and several types of sleep disturbances have been found to have significant genetic influences, as have traits of normal sleep, such as those evident in EEG patterns and the circadian sleep-wake cycle. The circadian sleep-wake cycle is based on a complex feedback loop of genetic transcription over a 24-h cycle. Restless legs syndrome (RLS) and periodic limb movements in sleep (PLMS) have familial aggregation, and several genes have a strong association with them. Recent genome-wide association studies have identified single nucleotide polymorphisms linked to RLS/PLMS, although none has a definite functional correlation. Narcolepsy/cataplexy are associated with HLA DQB1*0602 and a T-cell receptor α locus, although functional correlations have not been evident. Obstructive sleep apnea is a complex disorder involving multiple traits, such as anatomy of the oropharynx, ventilatory control, and traits associated with obesity. Although there is clear evidence of familial aggregation in the obstructive sleep apnea syndrome, no specific gene or locus has been identified for it. Angiotensin-converting enzyme has been proposed as a risk variant, but evidence is weak. Fatal familial insomnia and advanced sleep phase syndrome are sleep disorders with a definite genetic basis.
authors: Center for Sleep Medicine, Division of Pulmonary Medicine, Mayo Clinic, Scottsdale, AZ. Electronic address: parish.james@mayo.edu.
authors: James M
authors: JM
authors: Parish
mesh_terms: D002940:Circadian Rhythm / Q000502:physiology; D055106:Genome-Wide Association Study; D006801:Humans; D007107:Immune System / Q000502:physiology; D009290:Narcolepsy / Q000235:genetics / Q000276:immunology / Q000503:physiopathology; D012148:Restless Legs Syndrome / Q000235:genetics / Q000276:immunology / Q000503:physiopathology; D012890:Sleep / Q000235:genetics* / Q000276:immunology* / Q000502:physiology; D012891:Sleep Apnea Syndromes / Q000235:genetics / Q000276:immunology / Q000503:physiopathology; D012893:Sleep Wake Disorders / Q000235:genetics* / Q000276:immunology* / Q000503:physiopathology
references: Nat Genet. 2007 Aug;39(8):1000-6
references: 17637780
references: Cell. 2011 Jul 22;146(2):194-207
references: 21784243
references: Obes Facts. 2009;2(3):196-202
references: 20054225
references: Nat Genet. 2011 Jan;43(1):66-71
references: 21170044
references: Biol Psychiatry. 2008 Aug 15;64(4):344-8
references: 18405882
references: Sleep. 1983;6(3):179-85
references: 6684786
references: Paediatr Respir Rev. 2011 Dec;12(4):253-63
references: 22018041
references: JAMA. 2002 Sep 25;288(12):1471-2
references: 12243633
references: Curr Opin Genet Dev. 2009 Jun;19(3):212-9
references: 19481926
references: Chest. 2011 Feb;139(2):446-452
references: 21285061
references: Annu Rev Genet. 2008;42:361-88
references: 18983259
references: Ann N Y Acad Sci. 2008;1129:323-9
references: 18591491
references: Behav Genet. 1997 Jul;27(4):325-51
references: 9519560
references: Brain. 2003 Jun;126(Pt 6):1485-92
references: 12764067
references: Hum Mol Genet. 2006 Oct 15;15 Spec No 2:R271-7
references: 16987893
references: Am Rev Respir Dis. 1992 Feb;145(2 Pt 1):440-4
references: 1736754
references: Ann N Y Acad Sci. 2010 Apr;1193:48-59
references: 20398008
references: J Pediatr. 2011 Jan;158(1):77-82
references: 20846669
references: Sleep. 2010 Jul;33(7):869-74
references: 20614846
references: J Sleep Res. 1999 Jun;8 Suppl 1:23-9
references: 10389103
references: Am J Respir Crit Care Med. 2004 Dec 15;170(12):1349-53
references: 15447944
references: Ann Intern Med. 1995 Feb 1;122(3):174-8
references: 7810934
references: Ann Neurol. 2008 Oct;64(4):455-60
references: 18688819
references: N Engl J Med. 1986 Oct 16;315(16):997-1003
references: 3762620
references: Nat Rev Neurosci. 2009 Mar;10(3):199-210
references: 19209176
references: Annu Rev Med. 2011;62:447-60
references: 21073334
references: Sleep. 2012 Jan 01;35(1):97-101
references: 22215923
references: Psychosom Med. 2003 Sep-Oct;65(5):831-5
references: 14508028
references: Sleep. 2009 Nov;32(11):1507-11
references: 19928390
references: Neuron. 2000 Sep;27(3):469-74
references: 11055430
references: Neurology. 2004 Aug 24;63(4):664-8
references: 15326239
references: Proc Natl Acad Sci U S A. 1971 Sep;68(9):2112-6
references: 5002428
references: Nat Genet. 2009 Jun;41(6):708-11
references: 19412176
references: Nat Genet. 2008 Aug;40(8):946-8
references: 18660810
references: J Allergy Clin Immunol. 2005 Dec;116(6):1188-98
references: 16337444
references: Arch Neurol. 2002 Oct;59(10):1553-62
references: 12374492
references: JAMA. 2001 Jun 13;285(22):2888-90
references: 11401610
references: N Engl J Med. 2007 Aug 16;357(7):639-47
references: 17634447
references: Science. 2001 Feb 9;291(5506):1040-3
references: 11232563
references: Cell. 2007 Jan 12;128(1):59-70
references: 17218255
references: FASEB J. 1996 Apr;10(5):643-53
references: 8621064
references: Sleep. 1997 Nov;20(11):1012-20
references: 9456467
references: Front Biosci. 2003 May 01;8:d520-50
references: 12700031
references: Genetics. 2008 Mar;178(3):1147-55
references: 18385110
references: Am J Hum Genet. 2001 Dec;69(6):1266-70
references: 11704926
references: Sleep Med. 2004 Jun;5 Suppl 1:S2-8
references: 15301991
references: Neurology. 1998 Feb;50(2 Suppl 1):S16-22
references: 9484418
references: Sleep. 2007 Apr;30(4):531-3
references: 17520798
references: Eur Arch Psychiatry Clin Neurosci. 1992;242(1):53-6
references: 1390956
references: Cell. 2005 Nov 4;123(3):477-91
references: 16269338
references: Handb Clin Neurol. 2011;99:681-93
references: 21056223
references: Tissue Antigens. 1998 Jan;51(1):96-100
references: 9459509
references: Mov Disord. 2008 Feb 15;23(3):350-8
references: 18058820
references: Immunology. 2010 Mar;129(3):322-8
references: 20409153
references: N Engl J Med. 1978 Nov 2;299(18):969-73
references: 211413
references: Nat Genet. 2003 Mar;33 Suppl:228-37
references: 12610532
references: Hum Immunol. 2007 Jan;68(1):59-68
references: 17207713
references: Curr Pharm Des. 2008;14(32):3408-16
references: 19075717
references: Sleep. 2007 Jan;30(1):13-26
references: 17310860
references: Annu Rev Genomics Hum Genet. 2003;4:459-83
references: 14527309
references: Sleep. 2010 Jul;33(7):857-8
references: 20614841
references: Science. 1998 Jun 5;280(5369):1564-9
references: 9616112
references: J Clin Sleep Med. 2011 Oct 15;7(5 Suppl):S38-42
references: 22003330
references: Cell. 1999 Aug 20;98(4):437-51
references: 10481909
references: Sleep Med Clin. 2007;2(2):161-169
references: 19098992
references: Am J Respir Crit Care Med. 1995 Mar;151(3 Pt 1):682-7
references: 7881656
references: Sleep. 2012 Aug 01;35(8):1063-9
references: 22851802
references: J Biol Rhythms. 2004 Oct;19(5):339-47
references: 15536063
references: Eur Respir J. 2005 Oct;26(4):673-8
references: 16204600
references: Sleep. 2011 Nov 01;34(11):1461-8
references: 22043116
references: Sleep Med Rev. 2000 Dec;4(6):583-602
references: 12531037
references: Neuroimmunomodulation. 2005;12(3):131-40
references: 15905620
references: Science. 1994 Apr 29;264(5159):719-25
references: 8171325
references: J Clin Endocrinol Metab. 2004 Sep;89(9):4409-13
references: 15356039
references: Am J Hum Genet. 2001 Mar;68(3):686-99
references: 11179016
references: Sleep Med Rev. 2012 Apr;16(2):137-49
references: 21835655
references: Curr Opin Neurobiol. 2011 Dec;21(6):897-903
references: 21963829
references: Chest. 1995 Jun;107(6):1545-51
references: 7781344
references: Science. 2000 Apr 21;288(5465):483-92
references: 10775102