ABSTRACT
Sleep disorders arise by an interaction between the environment and the genetic makeup
of the individual but the relative contribution of nature and nurture varies with
diseases. At one extreme are the disorders with simple Mendelian patterns of inheritance
such as familial advanced sleep phase syndrome, and at the other extreme are diseases
such as insomnia, which can be associated with a multitude of medical and psychiatric
conditions. In this article, we review data on the relative contribution of genetic
and environmental factors in the pathogenesis of various sleep disorders. The understanding
of many of these disorders has been advanced by the study of sleep and circadian rhythms
in model laboratory organisms. We summarize this model system research and how it
relates to human sleep disorders. The current challenge in this field is the identification
of susceptibility genetic loci for complex diseases such as obstructive sleep apnea.
We anticipate such identification will increase our ability to assess risk for disease
before symptom onset and by doing so will shift the focus from treatment to prevention
of disease.
KEYWORDS
Sleep - genetics - circadian - homeostatic
REFERENCES
- 1
Peirson S, Foster R G.
Melanopsin: another way of signaling light.
Neuron.
2006;
49
331-339
- 2
Hara R, Wan K, Wakamatsu H et al..
Restricted feeding entrains liver clock without participation of the superchiasmatic
nucleus.
Genes Cells.
2001;
6
269-278
- 3
Konopka R J, Benzer S.
Clock mutants of Drosophila melanogaster
.
Proc Natl Acad Sci USA.
1971;
68
2112-2116
- 4
Allada R, Emery P, Takahashi J S, Roshbash M.
Stopping time: the genetics of fly and mouse circadian clocks.
Annu Rev Neurosci.
2001;
24
1091-1119
- 5
Toh K L, Jones C R, He Y et al..
An hPer2 phosphorylation site mutation in familial advanced sleep phase syndrome.
Science.
2001;
291
1040-1043
- 6
Jones C R, Campbell S S, Zone S E et al..
Familial advanced sleep-phase syndrome: a short-period circadian rhythm variant in
humans.
Nat Med.
1999;
5
1062-1065
- 7
Carpen J D, Archer S N, Skene D J, Smits M, von Schantz M.
A single-nucleotide polymorphism in the 5′-untranslated region of the hPER2 gene is
associated with diurnal preference.
J Sleep Res.
2005;
14
293-297
- 8
Xu Y, Padiath Q S, Shapiro R E et al..
Functional consequences of a CKIdelta mutation causing familial advanced sleep phase
syndrome.
Nature.
2005;
434
640-644
- 9
Czeisler C A, Duffy J F, Shanahan T L.
Stability, precision, and near 24-hour period of the human circadian pacemaker.
Science.
1999;
284
2177-2181
- 10
Dagan Y, Eisenstein M.
Circadian rhythm sleep disorders: toward a more precise definition and diagnosis.
Chronobiol Int.
1999;
16
213-222
- 11
Fukuda K.
Twins under shift work: a case study of sleep log data.
Percept Mot Skills.
1997;
84
931-937
- 12
Ancoli-Israel S, Schnierow B, Kelsoe J, Fink R.
A pedigree of one family with delayed sleep phase syndrome.
Chronobiol Int.
2001;
18
831-840
- 13
Horne J A, Ostberg O.
A self-assessment questionnaire to determine morningness-eveningness in human circadian
rhythms.
Int J Chronobiol.
1976;
4
97-110
- 14
Katzenberg D, Young T, Finn L et al..
A CLOCK polymorphism associated with human diurnal preference.
Sleep.
1998;
21
569-576
- 15
Robilliard D L, Archer S N, Arendt J et al..
The 3111 Clock gene polymorphism is not associated with sleep and circadian rhythmicity
in phenotypically characterized human subjects.
J Sleep Res.
2002;
11
305-312
- 16
Ebisawa T, Uchiyama M, Kajimura N et al..
Association of structural polymorphisms in the human period3 gene with delayed sleep
phase syndrome.
EMBO Rep.
2001;
2
342-346
- 17
Klein T, Martens H, Jan Dijk D K et al..
Circadian sleep regulation in the absence of light perception: chronic non-24-hour
circadian rhythm sleep disorder in a blind man with a regular 24-hour sleep-wake schedule.
Sleep.
1993;
16
333-343
- 18
Czeisler C A.
Commentary: evidence for melatonin as a circadian phase-shifting agent.
J Biol Rhythms.
1997;
12
618-623
- 19
Sack R L, Brandes R W, Kendall A R, Lewy A J.
Entrainment of free-running circadian rhythms by melatonin in blind people.
N Engl J Med.
2000;
343
1070-1077
- 20
Hohjoh H, Takasu M, Shishikura K.
Significant association of the arylalkylamine N-acetyltransferase (AA-NAT) gene with
delayed sleep phase syndrome.
Neurogenetics.
2003;
4
151-153
- 21
Borbely A A, Achermann P.
Sleep homeostasis and models of sleep regulation.
J Biol Rhythms.
1999;
14
557-568
- 22
Van Dongen H P, Baynard M D, Maislin G, Dinges D F.
Systematic interindividual differences in neurobehavioral impairment from sleep loss:
evidence of trait-like differential vulnerability.
Sleep.
2004;
27
423-433
- 23
Leproult R, Colecchia E F, Berardi A M, Stickgold R, Kosslyn S M, Van Cauter E.
Individual differences in subjective and objective alertness during sleep deprivation
are stable and unrelated.
Am J Physiol Regul Integr Comp Physiol.
2003;
284
R280-R290
- 24
Franken P, Chollet D, Tafti M.
The homeostatic regulation of sleep need is under genetic control.
J Neurosci.
2001;
21
2610-2621
- 25
Hendricks J C, Finn S M, Panckeri K A et al..
Rest in Drosophila is a sleep-like state.
Neuron.
2000;
25
129-138
- 26
Shaw P J, Cirelli C, Greenspan R J, Tononi G.
Correlates of sleep and waking in Drosophila melanogaster
.
Science.
2000;
287
1834-1837
- 27
Hendricks J C, Kirk D, Panckeri K, Miller M S, Pack A I.
Modafinil maintains waking in the fruit fly Drosophila melanogaster
.
Sleep.
2003;
26
139-146
- 28
Hendricks J C, Williams J A, Panckeri K et al..
A non-circadian role for cAMP signaling and CREB activity in Drosophila rest homeostasis.
Nat Neurosci.
2001;
4
1108-1115
- 29
Graves L A, Hellman K, Veasey S, Blendy J A, Pack A I, Abel T.
Genetic evidence for a role of CREB in sustained cortical arousal.
J Neurophysiol.
2003;
90
1152-1159
- 30
Cirelli C, Bushey D, Hill S et al..
Reduced sleep in Drosophila Shaker mutants.
Nature.
2005;
434
1087-1092
- 31
Pitman J L, McGill J J, Keegan K P, Allada R.
A dynamic role for the mushroom bodies in promoting sleep in Drosophila
.
Nature.
2006;
441
753-756
- 32
Joiner W J, Crocker A, White B H, Sehgal A.
Sleep in Drosophila is regulated by adult mushroom bodies.
Nature.
2006;
441
757-760
- 33
Hori A, Hirose G.
Twin studies on parasomnias.
Proceedings of the World Federation of Sleep Research Societies.
1995;
324
24A
- 34
Roth B, Buuhova S, Berkova L.
Familial sleep paralysis.
Schweiz Arch Neurol Neurochir Psychiatr.
1968;
102
321-330
- 35
Goode G B.
Sleep paralysis.
Arch Neurol.
1962;
6
228-234
- 36
Mignot E.
Genetic and familial aspects of narcolepsy.
Neurology.
1998;
50
s16-s22
- 37
Scammell T E.
The frustrating and mostly fruitless search for an autoimmune cause for narcolepsy.
Sleep.
2006;
29
601-602
- 38
Lin L, Faraco J, Li R et al..
The sleep disorder canine narcolepsy is caused by a mutation in the hypocretin (orexin)
receptor 2 gene.
Cell.
1999;
98
365-376
- 39
Peyron C, Tighe D K, van den Pol A N et al..
Neurons containing hypocretin (orexin) project to multiple neuronal systems.
J Neurosci.
1998;
18
9996-10015
- 40
Chemelli R M, Willie J T, Sinton C et al..
Narcolepsy in orexin knockout mice: molecular genetics of sleep regulation.
Cell.
1999;
98
437-451
- 41
Nishino S, Ripley B, Overeem S, Lammers G J, Mignot E.
Hypocretin (orexin) deficiency in human narcolepsy.
Lancet.
2000;
355
39-40
- 42
Peyron C, Faraco J, Rogers W 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
- 43
Thannickal T C, Moore R Y, Nienhuis R et al..
Reduced number of hypocretin neurons in human narcolepsy.
Neuron.
2000;
27
469-474
- 44
Crocker A, Espana R A, Papadopoulou M et al..
Concomitant loss of dynorphin, NARP, and orexin in narcolepsy.
Neurology.
2005;
65
1184-1188
- 45
Mignot E, Lammers G J, Ripley B et al..
The role of cerebrospinal fluid hypocretin measurement in the diagnosis of narcolepsy
and other hypersomnias.
Arch Neurol.
2002;
59
1553-1562
- 46
Mignot E, Hayduk R, Black J, Grumet F C, Guilleminault C.
HLA DQB1*0602 is associated with cataplexy in 509 narcoleptic patients.
Sleep.
1997;
20
1012-1020
- 47
Dauvilliers Y, Carlander B, Molinari N et al..
Month of birth as a risk factor for narcolepsy.
Sleep.
2003;
26
663-665
- 48
Saper C B, Chou T C, Scammell T E.
The sleep switch: hypothalamic control of sleep and wakefulness.
Trends Neurosci.
2001;
24
726-731
- 49
Lu J, Sherman D, Devor M, Saper C B.
A putative flip-flop switch for control of REM sleep.
Nature.
2006;
441
589-594
- 50 Broughton R.
NREM parasomnias. In: Kryger MH, Roth T, Dement WC Principles and Practice of Sleep Medicine. Philadelphia;
W.B. Saunders 2000: 693-706
- 51
Fisher C, Kahn E, Edwards A, Davis D M.
A psychophysiological study of nightmares and night terrors: I. Physiological aspects
of the stage 4 night terror.
J Nerv Ment Dis.
1973;
157
75-98
- 52 Mahowald M.
Arousal and sleep-wake transition parasomnias. In: Lee-Chiong TL, Mahowald MW, Carskadon MA Sleep Medicine. Philadelphia; Hanley
and Belfus 2002: 207-213
- 53
Rosen G M, Ferber R, Mahowald M W.
Evaluation of parasomnias in children.
Child Adolesc Psychiatr Clin N Am.
1996;
5
601-616
- 54
Mason II T B, Pack A I.
Sleep terrors in childhood.
J Pediatr.
2005;
147
388-392
- 55
Hallstrom T.
Night terror in adults through three generations.
Acta Psychiatr Scand.
1972;
48
350-352
- 56
Kales A, Soldatos C R, Bixler E O et al..
Hereditary factors in sleepwalking and night terrors.
Br J Psychiatry.
1980;
137
111-118
- 57
Ooki S.
Statistical genetic analysis of some problem behaviors during sleep in childhood:
estimation of genetic and environmental factors influencing multiple health phenomena
simultaneously.
Nippon Eiseigaku Zasshi.
2000;
55
489-499
- 58
Lecendreux M, Bassetti C, Dauvilliers Y, Mayer G, Neidhart E, Tafti M.
HLA and genetic susceptibility to sleepwalking.
Mol Psychiatry.
2003;
8
114-117
- 59
Hublin C, Kaprio J, Partinen M, Heikkila K, Koskenvuo M.
Prevalence and genetics of sleepwalking: a population-based twin study.
Neurology.
1997;
48
177-181
- 60
Mahowald M W, Schenck C H, Rosen G M, Hurwitz T D.
The role of a sleep disorder center in evaluating sleep violence.
Arch Neurol.
1992;
49
604-607
- 61
Owens J, Spirito A, Nobile C, Arrigan M.
Incidence of parasomnias in children with obstructive sleep apnea.
Sleep.
1997;
20
1193-1196
- 62
Goodwin J L, Kaemingk K L, Fregosi R F et al..
Parasomnias and sleep disordered breathing in Caucasian and Hispanic children: the
Tucson children's assessment of sleep apnea study.
BMC Med.
2004;
2
14
- 63
Guilleminault C, Palombini L, Pelayo R, Chervin R D.
Sleepwalking and sleep terrors in prepubertal children: what triggers them?.
Pediatrics.
2003;
111
e17-e25
- 64
Schenck C H, Mahowald M W.
Rapid eye movement sleep parasomnias.
Neurol Clin.
2005;
23
1107-1126
- 65
Schenck C H, Bundlie S R, Ettinger M G, Mahowald M W.
Chronic behavioral disorders of human REM sleep: a new category of parasomnia.
Sleep.
1986;
9
293-308
- 66
Sheldon S H.
Parasomnias in childhood.
Pediatr Clin North Am.
2004;
51
69-88
- 67
Montagna P.
Sleep-related non epileptic motor disorders.
J Neurol.
2004;
251
781-794
- 68
Postuma R B, Lang A E, Massicotte-Marquez J, Montplaisir J.
Potential early markers of Parkinson disease in idiopathic REM sleep behavior disorder.
Neurology.
2006;
66
845-851
- 69
Gagnon J F, Postuma R B, Mazza S, Doyon J, Montplaisir J.
Rapid-eye-movement sleep behaviour disorder and neurodegenerative diseases.
Lancet Neurol.
2006;
5
424-432
- 70
Hendricks J C, Morrison A R, Mann G L.
Different behaviors during paradoxical sleep without atonia depend on pontine lesion
site.
Brain Res.
1982;
239
81-105
- 71
Schenck C H, Bundlie S R, Mahowald M W.
Delayed emergence of a parkinsonian disorder in 38% of 29 older men initially diagnosed
with idiopathic rapid eye movement sleep behaviour disorder.
Neurology.
1996;
46
388-393
- 72
Boeve B F, Silber M H, Ferman T J, Lucas J A, Parisi J E.
Association of REM sleep behavior disorder and neurodegenerative disease may reflect
an underlying synucleinopathy.
Mov Disord.
2001;
16
622-630
- 73
Schapira A H.
Etiology of Parkinson's disease.
Neurology.
2006;
66(suppl 4)
S10-S23
- 74
Ekbom K A.
Restless legs: a clinical study.
Acta Med Scand.
1945;
158
1-123
- 75
Phillips B, Young T, Finn L, Asher K, Hening W A, Purvis C.
Epidemiology of restless leg syndrome in adults.
Arch Intern Med.
2000;
160
2137-2141
- 76
Lavigne G J, Montplaisir J.
Restless legs syndrome and sleep bruxism.
Sleep.
1994;
17
739-743
- 77
Rothdach A J, Trenkwalder C, Haberstock J, Keil U, Berger K.
Prevalence and risk factors of RLS in an elderly population: the MEMO study. Memory
and Morbidity in Augsburg Elderly.
Neurology.
2000;
54
1064-1068
- 78
Walters A S.
Toward a better definition of the restless legs syndrome. The International Restless
Legs Syndrome Study Group.
Mov Disord.
1995;
10
634-642
- 79
Allen R P, Picchietti D L, Hening W A, Trenkwalder C, Walters A S, Montplaisir J.
Restless leg syndrome diagnostic criteria, special considerations, and epidemiology.
A report from the restless leg syndrome diagnosis and epidemiology workshop at the
National Institutes of Health.
Sleep Med.
2003;
4
101-119
- 80
Desautels A, Turecki G, Montplaisir J et al..
Restless legs syndrome: confirmation of linkage to chromosome 12q, genetic heterogeneity,
and evidence of complexity.
Arch Neurol.
2005;
62
591-596
- 81
Ekbom K A.
Restless legs syndrome.
Neurology.
1960;
10
868-873
- 82
Sun E R, Chen C A, Ho G, Earley C J, Allen R P.
Iron and the restless legs syndrome.
Sleep.
1998;
21
371-377
- 83
Goodman J D, Brodie C, Ayida G A.
Restless leg syndrome in pregnancy.
BMJ.
1988;
297
1101-1102
- 84
Connor J R, Boyer P J, Menzies S L et al..
Neuropathological examination suggests impaired brain iron acquisition in restless
legs syndrome.
Neurology.
2003;
61
304-309
- 85
Allen R P, Barker P B, Wehrl F, Song H K, Earley C J.
MRI measurement of brain iron in patients with restless legs syndrome.
Neurology.
2001;
56
263-265
- 86
Earley C J, Connor J R, Beard J L, Malecki E A, Epstein D K, Allen R P.
Abnormalities in CSF concentrations of ferritin and transferrin in restless legs syndrome.
Neurology.
2000;
54
1698-1700
- 87
Mizuno S, Mihara T, Miyaoka T, Inagaki T, Horiguchi J.
CSF iron, ferritin and transferrin levels in restless legs syndrome.
J Sleep Res.
2005;
14
43-47
- 88
Nordlander N B.
Therapy in restless legs.
Acta Med Scand.
1953;
145
453-457
- 89
Earley C J, Heckler D, Allen R P.
Repeated IV doses of iron provides effective supplemental treatment of restless legs
syndrome.
Sleep Med.
2005;
6
301-305
- 90
Sowers J R, Vlachakis N.
Circadian variation in plasma dopamine levels in man.
J Endocrinol Invest.
1984;
7
341-345
- 91
Weber M, Lauterburg T, Tobler I, Burgunder J M.
Circadian patterns of neurotransmitter related gene expression in motor regions of
the rat brain.
Neurosci Lett.
2004;
358
17-20
- 92
Clemens S, Sawchuk M A, Hochman S.
Reversal of the circadian expression of tyrosine hydroxylase but not nitric oxide
synthase levels in the spinal cord of dopamine D(3) knockout mice.
Neuroscience.
2005;
133
353-357
- 93
Bara-Jimenez W, Aksu M, Graham B, Sato S, Hallett M.
Periodic limb movements in sleep: state-dependent excitability of the spinal flexor
reflex.
Neurology.
2000;
54
1609-1616
- 94
Lu J, Jhou T C, Saper C B.
Identification of wake-active dopaminergic neurons in the ventral periaqueductal gray
matter.
J Neurosci.
2006;
26
193-202
- 95
Allen R.
Dopamine and iron in the pathophysiology of restless legs syndrome (RLS).
Sleep Med.
2004;
5
385-391
- 96
Desautels A, Turecki G, Montplaisir J et al..
Dopaminergic neurotransmission and restless leg syndrome: a genetic association study.
Neurology.
2001;
57
1304-1306
- 97
Ambrosetto C, Lugaresi E, Coccagna G, Tasssinari C A.
Clinical and polygraphic remarks in the syndrome of restless legs.
Riv Patol Nerv Ment.
1965;
86
244-252
- 98
Bornstein B.
Restless legs.
Psychiatria et Neurologia.
1961;
141
165-201
- 99 Montagna P, Coccagna G, Ciriguotta F, Luganesi E.
Familial restless legs syndrome. In: Guilleminault C, Lugaresi E Sleep/Wake Disorders: Natural History, Epidemiology,
and Long-Term Evolution. New York; Raven Press 1983: 231-235
- 100
Hening W A, Washburn T, Somel D, LeSage S, Allen R P, Earley C J.
RLS patients with younger age of onset have a higher frequency of affected relatives.
Neurology.
2003;
60(suppl 1)
S05.004
- 101
Ondo W G, Vuong K D, Wang Q.
Restless leg syndrome in monozygotic twins: clinical correlates.
Neurology.
2000;
55
1404-1406
- 102
Trenkwalder C, Seidel V C, Gasser T, Oertel W H.
Clinical symptoms and possible anticipation in a large kindred of familial restless
legs syndrome.
Mov Disord.
1996;
11
389-394
- 103
Lazzarini A, Walters A S, Hickey K et al..
Studies of penetrance and anticipation in five autosomal-dominant restless legs syndrome
pedigrees.
Mov Disord.
1999;
14
111-116
- 104
Winkelmann J, Muller-Myhsok B, Wittchen H U et al..
Complex segregation analysis of restless legs syndrome provides evidence for an autosomal
dominant mode of inheritance in early age at onset families.
Ann Neurol.
2002;
52
297-302
- 105
Desautels A, Turecki G, Montplaisir J, Saqueira A, Verner A, Rouleau G A.
Identification of a major susceptibility locus for restless legs syndrome on chromosome
12q.
Am J Hum Genet.
2001;
69
1266-1270
- 106
Walters A S, Picchietti D L, Hening W A, Lazzarini A.
Variable expressivity in familial restless leg syndrome.
Arch Neurol.
1990;
47
1219-1220
- 107
Kock N, Culjkovic B, Maniak S et al..
Mode of inheritance and susceptibility locus for restless legs syndrome, on chromosome
12q.
Am J Hum Genet.
2002;
71
205-208
- 108
Bonati M T, Ferini-Strambi L, Aridon P, Oldani A, Zucconi M, Casari G.
Autosomal dominant restless legs syndrome maps to chromosome 14q.
Brain.
2003;
126
1485-1492
- 109
Chen S, Ondo W G, Rao S, Li L, Chen Q, Wang Q.
Genomewide linkage scan identifies a novel susceptibility locus for restless leg syndrome
on chromosome 9p.
Am J Hum Genet.
2004;
74
876-885
- 110
Desautels A, Turecki G, Montplaisir J et al..
Evidence for a genetic association between monoamine oxidase A and restless leg syndrome.
Neurology.
2002;
59
215-219
- 111
Gemignani F, Marbini A, Di Giovanni G, Salih S, Terzano M G.
Charcot-Marie-Tooth disease type 2 with restless legs syndrome.
Neurology.
1999;
52
1064-1066
- 112
Konieczny M, Bauer P, Tomiuk J et al..
CAG repeats in restless legs syndrome.
Am J Med Genet B Neuropsychiatr Genet.
2006;
141
173-176
- 113
Roth T.
Prevalence, associated risks, and treatment patterns of insomnia.
J Clin Psychiatry.
2005;
66(suppl 9)
10-13
- 114
Stepanski E J, Rybarczyk B.
Emerging research on the treatment and etiology of secondary or comorbid insomnia.
Sleep Med Rev.
2006;
10
7-18
- 115
Fava M.
Daytime sleepiness and insomnia as correlates of depression.
J Clin Psychiatry.
2004;
65(suppl 16)
27-32
- 116
Dauvilliers Y, Morin C, Cervena K et al..
Family studies in insomnia.
J Psychosom Res.
2005;
58
271-278
- 117
Gambetti P, Parchi P.
Insomnia in prion diseases: sporadic and familial.
N Engl J Med.
1999;
340
1675-1677
- 118
Prusiner S B.
Prions.
Proc Natl Acad Sci USA.
1998;
95
13363-13383
- 119
Dauvilliers Y, Cervena K, Carlander B et al..
Dissociation in circadian rhythms in a pseudohypersomnia form of fatal familial insomnia.
Neurology.
2004;
63
2416-2418
- 120
Lugaresi E, Medori R, Baruzzi A et al..
Fatal familial insomnia and dysautonomia with selective degeneration of thalamic nuclei.
N Engl J Med.
1986;
315
997-1003
- 121
Manetto V, Medori R, Cortelli P et al..
Fatal familial insomnia: clinical and pathologic study of 5 new cases.
Neurology.
1992;
42
312-319
- 122
Goldfarb L G, Petersen R B, Tabaton M et al..
Fatal familial insomnia and familial Creutzfeldt-Jakob disease: disease phenotype
determined by a DNA polymorphism.
Science.
1992;
258
806-808
- 123
Montagna P, Cortelli P, Avoni P et al..
Clinical features of fatal familial insomnia: phenotypic variability in relation to
a polymorphism at codon 129 of the prion protein gene.
Brain Pathol.
1998;
8
515-520
- 124
Mastrianni J A, Nixon R, Layzer R et al..
Prion protein conformation in a patient with sporadic fatal insomnia.
N Engl J Med.
1999;
340
1630-1638
- 125
Parchi P, Capellari S, Chin S et al..
A subtype of sporadic prion disease mimicking fatal familial insomnia.
Neurology.
1999;
52
1757-1763
- 126
Landolt H P, Glatzel M, Blattler T et al..
Sleep-wake disturbances in sporadic Creutzfeldt-Jakob disease.
Neurology.
2006;
66
1418-1424
- 127
Tobler I, Deboer T, Fischer M.
Sleep and sleep regulation in normal and prion protein-deficient mice.
J Neurosci.
1997;
17
1869-1879
- 128
Bazil C W.
Nocturnal seizures.
Semin Neurol.
2004;
24
293-300
- 129
Herman S T, Walczak T S, Bazil C W.
Distribution of partial seizures during the sleep-wake cycle: differences by seizure
onset site.
Neurology.
2001;
56
1453-1459
- 130
Malow B A, Weatherwax K J, Chervin R D et al..
Identification and treatment of obstructive sleep apnea in adults and children with
epilepsy: a prospective pilot study.
Sleep Med.
2003;
4
509-515
- 131
Malow B A.
Sleep deprivation and epilepsy.
Epilepsy Curr.
2004;
4
193-195
- 132
Vadlamudi L, Kjeldsen M J, Corey L A et al..
Analyzing the etiology of benign Rolandic epilepsy: a multicenter twin collaboration.
Epilepsia.
2006;
47
550-555
- 133
Provini F, Plazzi G, Tinuper P, Vandi S, Lugaresi E, Montagna P.
Nocturnal frontal lobe epilepsy: a clinical and polygraphic overview of 100 consecutive
cases.
Brain.
1999;
122
1017-1031
- 134
Provini F, Plazzi G, Lugaresi E.
From nocturnal paroxysmal dystonia to nocturnal frontal lobe epilepsy.
Clin Neurophysiol.
2000;
111(suppl 2)
S2-S8
- 135
Hirose S, Iwata H, Akiyoshi H et al..
A novel mutation of CHRNA4 responsible for autosomal dominant nocturnal frontal lobe
epilepsy.
Neurology.
1999;
53
1749-1753
- 136
De Fusco M, Becchetti A, Patrignani A et al..
The nicotinic receptor beta 2 subunit is mutant in nocturnal frontal lobe epilepsy.
Nat Genet.
2000;
26
275-276
- 137
Bertrand D, Picard F, Le Hellard S et al..
How mutations in the nAChRs can cause ADNFLE epilepsy.
Epilepsia.
2002;
43(suppl 5)
112-122
- 138
Combi R, Dalpra L, Ferini-Strambi L, Tenchini M L.
Frontal lobe epilepsy and mutations of the corticotropin-releasing hormone gene.
Ann Neurol.
2005;
58
899-904
- 139
Pack A I.
Advances in sleep-disordered breathing.
Am J Respir Crit Care Med.
2006;
173
7-15
- 140
Young T, Palta M, Dempsey J, Skatrud J, Weber S, Badr S.
The occurrence of sleep-disordered breathing among middle-aged adults.
N Engl J Med.
1993;
328
1230-1235
- 141
Young T, Peppard P E, Gottlieb D J.
Epidemiology of obstructive sleep apnea: a population health perspective.
Am J Respir Crit Care Med.
2002;
165
1217-1239
- 142
Young T, Skatrud J, Peppard P E.
Risk factors for obstructive sleep apnea in adults.
JAMA.
2004;
291
2013-2016
- 143
Bixler E O, Vgontzas A N, Lin H M et al..
Prevalence of sleep-disordered breathing in women: effects of gender.
Am J Respir Crit Care Med.
2001;
163
608-613
- 144
Peppard P E, Young T, Palta M, Dempsey J, Skatrud J.
Longitudinal study of moderate weight change and sleep-disordered breathing.
JAMA.
2000;
284
3015-3021
- 145
Pepperell J C, Ramdassingh-Dow S, Crosthwaite N et al..
Ambulatory blood pressure after therapeutic and subtherapeutic nasal continuous positive
airway pressure for obstructive sleep apnoea: a randomised parallel trial.
Lancet.
2002;
359
204-210
- 146
Becker H F, Jerrentrup A, Ploch T et al..
Effect of nasal continuous positive airway pressure treatment on blood pressure in
patients with obstructive sleep apnea.
Circulation.
2003;
107
68-73
- 147
Mehra R, Benjamin E J, Shahar E et al..
Association of nocturnal arrhythmias with sleep-disordered breathing: The Sleep Heart
Health Study.
Am J Respir Crit Care Med.
2006;
173
910-916
- 148
Marin J M, Carrizo S J, Vicente E, Agusti A G.
Long-term cardiovascular outcomes in men with obstructive sleep apnoea-hypopnoea with
or without treatment with continuous positive airway pressure: an observational study.
Lancet.
2005;
365
1046-1053
- 149
Ip M S, Lam B, Ng M M, Lam W K, Tsang K W, Lam K S.
Obstructive sleep apnea is independently associated with insulin resistance.
Am J Respir Crit Care Med.
2002;
165
670-676
- 150
Punjabi N M, Sorkin J D, Katzel L I, Goldberg A P, Schwartz A R, Smith P L.
Sleep-disordered breathing and insulin resistance in middle-aged and overweight men.
Am J Respir Crit Care Med.
2002;
165
677-682
- 151
Punjabi N M, Shahar E, Redline S, Gottlieb D J, Givelber R, Resnick H E.
Sleep-disordered breathing, glucose intolerance, and insulin resistance: the Sleep
Heart Health Study.
Am J Epidemiol.
2004;
160
521-530
- 152
Babu A R, Herdegen J, Fogelfeld L, Shott S, Mazzone T.
Type 2 diabetes, glycemic control, and continuous positive airway pressure in obstructive
sleep apnea.
Arch Intern Med.
2005;
165
447-452
- 153
Strohl K P, Saunders N A, Feldman N T, Hallett M.
Obstructive sleep apnea in family members.
N Engl J Med.
1978;
299
969-973
- 154
Redline S, Tosteson T, Tishler P V, Carskadon M A, Millman R P.
Studies in the genetics of obstructive sleep apnea: familial aggregation of symptoms
associated with sleep-related breathing disturbances.
Am Rev Respir Dis.
1992;
145
440-444
- 155
Redline S, Tishler P V, Tosteson T D et al..
The familial aggregation of obstructive sleep apnea.
Am J Respir Crit Care Med.
1995;
151
682-687
- 156
Mathur R, Douglas N J.
Family studies in patients with the sleep apnea-hypopnea syndrome.
Ann Intern Med.
1995;
122
174-178
- 157
Pillar G, Lavie P.
Assessment of the role of inheritance in sleep apnea syndrome.
Am J Respir Crit Care Med.
1995;
151
688-691
- 158
Gislason T, Johannsson J H, Haraldsson A et al..
Familial predisposition and cosegregation analysis of adult obstructive sleep apnea
and the sudden infant death syndrome.
Am J Respir Crit Care Med.
2002;
166
833-838
- 159
Schwab R J.
Genetic determinants of upper airway structures that predispose to obstructive sleep
apnea.
Respir Physiol Neurobiol.
2005;
147
289-298
- 160 Schwab R J, Arens R, Pack A.
Sleep apnea. In: Lipson DA, van Beek EJR Functional Lung Imaging. Vol. 200: Lung Biology in Health
and Disease. Boca Raton; Taylor and Francis 2005: 513-557
- 161
Horner R L, Mohiaddin R H, Lowell D G et al..
Sites and sizes of fat deposits around the pharynx in obese patients with obstructive
sleep apnoea and weight matched controls.
Eur Respir J.
1989;
2
613-622
- 162
Miles P G, Vig P S, Weyant R J, Forrest T D, Rockette Jr H E.
Craniofacial structure and obstructive sleep apnea syndrome: a qualitative analysis
and meta-analysis of the literature.
Am J Orthod Dentofacial Orthop.
1996;
109
163-172
- 163
Lowe A A, Fleetham J A, Adachi S, Ryan C F.
Cephalometric and computed tomographic predictors of obstructive sleep apnea severity.
Am J Orthod Dentofacial Orthop.
1995;
107
589-595
- 164
Guilleminault C, Partinen M, Hollman K, Powell N, Stoohs R.
Familial aggregates in obstructive sleep apnea syndrome.
Chest.
1995;
107
1545-1551
- 165
Schwab R J, Pasirstein M, Pierson R et al..
Identification of upper airway anatomic risk factors for obstructive sleep apnea with
volumetric magnetic resonance imaging.
Am J Respir Crit Care Med.
2003;
168
522-530
- 166
Schwab R J, Pasirstein M, Kaplan L et al..
Family aggregation of upper airway soft tissue structures in normal subjects and patients
with sleep apnea.
Am J Respir Crit Care Med.
2006;
173
453-463
- 167
Bell C G, Walley A J, Froguel P.
The genetics of human obesity.
Nat Rev Genet.
2005;
6
221-234
- 168
Stunkard A J, Foch T T, Hrubec Z.
A twin study of human obesity.
JAMA.
1986;
256
51-54
- 169
Sorensen T I, Price R A, Stunkard A J, Schulsinger F.
Genetics of obesity in adult adoptees and their biological siblings.
BMJ.
1989;
298
87-90
- 170
Borecki I B, Rice T, Perusse L, Bouchard C, Rao D C.
An exploratory investigation of genetic linkage with body composition and fatness
phenotypes: the Quebec Family Study.
Obes Res.
1994;
2
213-219
- 171
Borecki I B, Rice T, Perusse L, Bouchard C, Rao D C.
Major gene influence on the propensity to store fat in trunk versus extremity depots:
evidence from the Quebec Family Study.
Obes Res.
1995;
3
1-8
- 172
Rice T, Perusse L, Bouchard C, Rao D C.
Familial clustering of abdominal visceral fat and total fat mass: the Quebec Family
Study.
Obes Res.
1996;
4
253-261
- 173
Kadotani H, Kadotani T, Young T et al..
Association between apolipoprotein E epsilon4 and sleep-disordered breathing in adults.
JAMA.
2001;
285
2888-2890
- 174
Gottlieb D J, DeStefano A L, Foley D J et al..
APOE epsilon4 is associated with obstructive sleep apnea/hypopnea: the Sleep Heart
Health Study.
Neurology.
2004;
63
664-668
- 175
Foley D J, Masaki K, White L, Redline S.
Relationship between apolipoprotein E epsilon4 and sleep-disordered breathing at different
ages.
JAMA.
2001;
286
1447-1448
- 176
Saarelainen S, Lehtimaki T, Kallonen E, Laasonen K, Poussa T, Nieminen M M.
No relation between apolipoprotein E alleles and obstructive sleep apnea.
Clin Genet.
1998;
53
147-148
- 177
Larkin E K, Patel S R, Redline S, Mignot E, Elston R C, Hallmayer J.
Apolipoprotein E and obstructive sleep apnea: evaluating whether a candidate gene
explains a linkage peak.
Genet Epidemiol.
2006;
30
101-110
- 178
O'Hara R, Schroder C M, Kraemer H C et al..
Nocturnal sleep apnea/hypopnea is associated with lower memory performance in APOE
epsilon4 carriers.
Neurology.
2005;
65
642-644
- 179
Sakai K, Takada T, Nakayama H et al..
Serotonin-2A and 2C receptor gene polymorphisms in Japanese patients with obstructive
sleep apnea.
Intern Med.
2005;
44
928-933
- 180
Riha R L, Brander P, Vennelle M et al..
Tumour necrosis factor-alpha (-308) gene polymorphism in obstructive sleep apnoea-hypopnoea
syndrome.
Eur Respir J.
2005;
26
673-678
- 181
Vgontzas A N, Zoumakis E, Lin H M, Bixler E O, Trakada G, Chrousos G P.
Marked decrease in sleepiness in patients with sleep apnea by etanercept, a tumor
necrosis factor-alpha antagonist.
J Clin Endocrinol Metab.
2004;
89
4409-4413
- 182
Palmer L J, Buxbaum S G, Larkin E et al..
A whole-genome scan for obstructive sleep apnea and obesity.
Am J Hum Genet.
2003;
72
340-350
- 183
Palmer L J, Buxbaum S G, Larkin E K et al..
Whole genome scan for obstructive sleep apnea and obesity in African-American families.
Am J Respir Crit Care Med.
2004;
169
1314-1321
- 184
Buxbaum S G, Elston R C, Tishler P V, Redline S.
Genetics of the apnea hypopnea index in Caucasians and African Americans: I. Segregation
analysis.
Genet Epidemiol.
2002;
22
243-253
- 185
Ginsburg G S, Donahue M P, Newby L K.
Prospects for personalized cardiovascular medicine: the impact of genomics.
J Am Coll Cardiol.
2005;
46
1615-1627
Allan I PackM.B. Ch.B. Ph.D.
Center for Sleep and Respiratory Neurobiology, University of Pennsylvania School of
Medicine
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