The genetics of sleep apnea.

Obstructive sleep apnea hypopnea syndrome (OSAHS) is a complex chronic condition that is undoubtedly influenced by multiple factors. Accumulating data suggest that there are strong genetic underpinnings for this condition. It has been estimated that approximately 40% of the variance in the apnea hypopnea index (AHI) may be explained by familial factors. It is likely that genetic factors associated with craniofacial structure, body fat distribution and neural control of the upper airway muscles interact to produce the OSAHS phenotype. Although the role of specific genes that influence the development of OSAHS have not yet been identified, current research in rodents suggests that several genetic systems may be important. In this chapter, we shall first define the OSAHS phenotype, and then review the evidence that suggests an underlying genetic basis of OSAHS, the risk factors for OSAHS that may be inherited, and potential candidate genes.

[1]  N. Anthonisen,et al.  Familial aspects of ventilatory control in patients with chronic obstructive pulmonary disease. , 2015, The American review of respiratory disease.

[2]  Y. Kawakami,et al.  Familial factors affecting arterial blood gas values and respiratory chemosensitivity in chronic obstructive pulmonary disease. , 2015, The American review of respiratory disease.

[3]  J. Fleetham,et al.  Cephalometric and demographic characteristics of obstructive sleep apnea: an evaluation with partial least squares analysis. , 2009, The Angle orthodontist.

[4]  Sebastiaan Overeem,et al.  Hypocretin (orexin) deficiency in human narcolepsy , 2000, The Lancet.

[5]  J. Hebebrand,et al.  Phenotypes in three pedigrees with autosomal dominant obesity caused by haploinsufficiency mutations in the melanocortin-4 receptor gene. , 1999, American journal of human genetics.

[6]  C. Tankersley Genetic control of ventilation: what are we learning from murine models? , 1999, Current opinion in pulmonary medicine.

[7]  S. Redline,et al.  Recognition and consequences of obstructive sleep apnea hypopnea syndrome. , 1999, Clinics in chest medicine.

[8]  S. Redline,et al.  Obstructive sleep apnea/ hypopnea syndrome , 1999, Current treatment options in neurology.

[9]  H. Gershenfeld,et al.  The effects of leptin on REM sleep and slow wave deltain rats are reversed by food deprivation , 1999, Journal of sleep research.

[10]  Jon T. Willie,et al.  Narcolepsy in orexin Knockout Mice Molecular Genetics of Sleep Regulation , 1999, Cell.

[11]  Daniel J Buysse,et al.  Sleep–Related Breathing Disorders in Adults: Recommendations for Syndrome Definition and Measurement Techniques in Clinical Research , 2000 .

[12]  X. Huang,et al.  Angiotensin I-converting enzyme gene polymorphism in Chinese patients with obstructive sleep apnea syndrome. , 1999, Chinese medical journal.

[13]  Daniel J Buysse,et al.  Sleep-related breathing disorders in adults: recommendations for syndrome definition and measurement techniques in clinical research. The Report of an American Academy of Sleep Medicine Task Force. , 1999, Sleep.

[14]  D. Seals,et al.  Leptin is released from the human brain: influence of adiposity and gender. , 1999, The Journal of clinical endocrinology and metabolism.

[15]  P. L. Smith,et al.  Leptin prevents respiratory depression in obesity. , 1999, American journal of respiratory and critical care medicine.

[16]  S. Redline,et al.  Risk factors for sleep-disordered breathing in children. Associations with obesity, race, and respiratory problems. , 1999, American journal of respiratory and critical care medicine.

[17]  H. Shimizu,et al.  Expression of leptin receptor in lung: leptin as a growth factor. , 1999, European journal of pharmacology.

[18]  W. Tan,et al.  Prevalence of snoring and sleep breathing-related disorders in Chinese, Malay and Indian adults in Singapore. , 1998, The European respiratory journal.

[19]  D. P. King,et al.  Role of the CLOCK protein in the mammalian circadian mechanism. , 1998, Science.

[20]  D. Allison,et al.  The search for human obesity genes. , 1998, Science.

[21]  A. Wakizaka,et al.  Point mutation in exon 12 of the receptor tyrosine kinase proto-oncogene RET in Ondine-Hirschsprung syndrome. , 1998, Pediatrics.

[22]  D. Cass,et al.  Congenital central hypoventilation syndrome and Hirschsprung’s disease , 1998, Archives of disease in childhood.

[23]  A. Munnich,et al.  Mutations of the RET-GDNF signaling pathway in Ondine's curse. , 1998, American journal of human genetics.

[24]  J. Blangero,et al.  Quantitative genetic analysis of arterial oxygen saturation in Tibetan highlanders. , 1997, Human biology.

[25]  C. Bouchard,et al.  Genetics of human obesity: research directions , 1997, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[26]  G. Boivin,et al.  TGFbeta2 knockout mice have multiple developmental defects that are non-overlapping with other TGFbeta knockout phenotypes. , 1997, Development.

[27]  S. Redline,et al.  Ventilatory-control abnormalities in familial sleep apnea. , 1997, American journal of respiratory and critical care medicine.

[28]  D. Allen,et al.  A circadian enhancer mediates PER-dependent mRNA cycling in Drosophila melanogaster , 1997, Molecular and cellular biology.

[29]  E. Mignot,et al.  PHARMACOLOGICAL ASPECTS OF HUMAN AND CANINE NARCOLEPSY , 1997, Progress in Neurobiology.

[30]  D. Papanicolaou,et al.  Elevation of plasma cytokines in disorders of excessive daytime sleepiness: role of sleep disturbance and obesity. , 1997, The Journal of clinical endocrinology and metabolism.

[31]  P. Lavie,et al.  Impaired respiratory response to resistive loading during sleep in healthy offspring of patients with obstructive sleep apnea. , 1997, American journal of respiratory and critical care medicine.

[32]  D. Shannon,et al.  RET proto-oncogene is important for the development of respiratory CO2 sensitivity. , 1997, Journal of the autonomic nervous system.

[33]  K. Chin,et al.  Heat shock protein 72 level decreases during sleep in patients with obstructive sleep apnea syndrome. , 1997, American journal of respiratory and critical care medicine.

[34]  W. Mitzner,et al.  Genetic control of differential baseline breathing pattern. , 1997, Journal of applied physiology.

[35]  John Blangero,et al.  A major quantitative trait locus determining serum leptin levels and fat mass is located on human chromosome 2 , 1997, Nature Genetics.

[36]  J. Champagnat,et al.  Reorganization of Pontine Rhythmogenic Neuronal Networks in Krox-20 Knockout Mice , 1996, Neuron.

[37]  M. Barbacid,et al.  Mice Lacking Brain-Derived Neurotrophic Factor Exhibit Visceral Sensory Neuron Losses Distinct from Mice Lacking NT4 and Display a Severe Developmental Deficit in Control of Breathing , 1996, The Journal of Neuroscience.

[38]  S. Redline,et al.  Recognition of obstructive sleep apnea. , 1996, American journal of respiratory and critical care medicine.

[39]  S. Schwartz,et al.  Congenital central hypoventilation syndrome: mutation analysis of the receptor tyrosine kinase RET. , 1996, American journal of medical genetics.

[40]  B. Ponder,et al.  GDNF signalling through the Ret receptor tyrosine kinase , 1996, Nature.

[41]  K. Chin,et al.  Effects of NCPAP therapy on fibrinogen levels in obstructive sleep apnea syndrome. , 1996, American journal of respiratory and critical care medicine.

[42]  Y. Yazaki,et al.  Impaired ventilatory responses to hypoxia and hypercapnia in mutant mice deficient in endothelin-1. , 1996, The American journal of physiology.

[43]  M G Hans,et al.  The association of sudden unexpected infant death with obstructive sleep apnea. , 1996, American journal of respiratory and critical care medicine.

[44]  S. Redline,et al.  Cephalometric assessment in obstructive sleep apnea. , 1996, American journal of orthodontics and dentofacial orthopedics : official publication of the American Association of Orthodontists, its constituent societies, and the American Board of Orthodontics.

[45]  P. Zabel,et al.  Obstructive sleep apnea syndrome and circadian rhythms of hormones and cytokines. , 1996, American journal of respiratory and critical care medicine.

[46]  S. Ancoli-Israel,et al.  Sleep-disordered breathing in African-American elderly. , 1995, American journal of respiratory and critical care medicine.

[47]  M Partinen,et al.  Familial aggregates in obstructive sleep apnea syndrome. , 1995, Chest.

[48]  P. Jennum,et al.  Snoring, family history, and genetic markers in men. The Copenhagen Male Study. , 1995, Chest.

[49]  G. Gallus,et al.  Snoring in twins. , 1995, Respiratory medicine.

[50]  P. Lavie,et al.  Assessment of the role of inheritance in sleep apnea syndrome. , 1995, American journal of respiratory and critical care medicine.

[51]  S. Redline,et al.  The familial aggregation of obstructive sleep apnea , 1995 .

[52]  R Mathur,et al.  Family Studies in Patients with the Sleep Apnea-Hypopnea Syndrome , 1995, Annals of Internal Medicine.

[53]  P. Chambon,et al.  Function of the retinoic acid receptors (RARs) during development (I). Craniofacial and skeletal abnormalities in RAR double mutants. , 1994, Development.

[54]  Y. Ouchi,et al.  Elevated blood pressure and craniofaclal abnormalities in mice deficient in endothelin-1 , 1994, Nature.

[55]  B. Pasini,et al.  Point mutations affecting the tyrosine kinase domain of the RET proto-oncogene in Hirschsprung's disease , 1994, Nature.

[56]  B. Ponder,et al.  Mutations of the RET proto-oncogene in Hirschsprung's disease , 1994, Nature.

[57]  S. Swaminathan,et al.  Comparison of peripheral chemoreceptor responses in monozygotic and dizygotic twin infants. , 1993, The American review of respiratory disease.

[58]  W. Mitzner,et al.  Hypercapnic ventilatory responses in mice differentially susceptible to acute ozone exposure. , 1993, Journal of applied physiology.

[59]  M. Marazita,et al.  Congenital central hypoventilation syndrome: inheritance and relation to sudden infant death syndrome. , 1993, American journal of medical genetics.

[60]  N. Douglas,et al.  Is the sleep apnoea/hypopnoea syndrome inherited? , 1993, Thorax.

[61]  S. Redline,et al.  Studies in the genetics of obstructive sleep apnea. Familial aggregation of symptoms associated with sleep-related breathing disturbances. , 1992, The American review of respiratory disease.

[62]  S. Redline,et al.  Measurement of sleep-related breathing disturbances in epidemiologic studies. Assessment of the validity and reproducibility of a portable monitoring device. , 1991, Chest.

[63]  S. Redline,et al.  A family study of sleep apnea. Anatomic and physiologic interactions. , 1990, Chest.

[64]  R. Pyeritz,et al.  Immunohistologic abnormalities of the microfibrillar-fiber system in the Marfan syndrome. , 1990, The New England journal of medicine.

[65]  L. Eaves,et al.  Genetic Analysis of Anthropometric Measures in 11-Year-Old Twins: The Medical College of Virginia Twin Study , 1990, Pediatric Research.

[66]  G. Mcclearn,et al.  The body-mass index of twins who have been reared apart. , 1990, The New England journal of medicine.

[67]  G. Bray 1989 McCollum Award lecture. Genetic and hypothalamic mechanisms for obesity--finding the needle in the haystack. , 1989, The American journal of clinical nutrition.

[68]  C. W. Sargent,et al.  Hypoxic and hypercapnic ventilatory responses in awake children with congenital central hypoventilation syndrome. , 1989, The American review of respiratory disease.

[69]  M. Khalifa,et al.  Congenital central hypoventilation syndrome in monozygotic twins. , 1988, The Journal of pediatrics.

[70]  J. Krieger,et al.  Craniofacial characteristics in patients with obstructive sleep apneas syndrome. , 1988, The Cleft palate journal.

[71]  M. Mitler,et al.  HLA-DR2 association with excessive somnolence in narcolepsy does not generalize to sleep apnea and is not accompanied by systemic autoimmune abnormalities. , 1988, Clinical immunology and immunopathology.

[72]  N J Douglas,et al.  The sleep hypopnea syndrome. , 1988, The American review of respiratory disease.

[73]  R. Ruff,et al.  Familial 'sleep apnea plus' syndrome , 1988, Neurology.

[74]  K. Strohl,et al.  Physiologic basis of therapy for sleep apnea. , 1987, The American review of respiratory disease.

[75]  J. Fleetham,et al.  Facial morphology and obstructive sleep apnea. , 1986, American journal of orthodontics and dentofacial orthopedics : official publication of the American Association of Orthodontists, its constituent societies, and the American Board of Orthodontics.

[76]  M Partinen,et al.  Obstructive sleep apneic patients have craniomandibular abnormalities. , 1986, Sleep.

[77]  J A Dempsey,et al.  A sleep-induced apneic threshold and its consequences. , 1986, The American review of respiratory disease.

[78]  P. L. Smith,et al.  Weight loss in mildly to moderately obese patients with obstructive sleep apnea. , 1985, Annals of internal medicine.

[79]  C. Guilleminault,et al.  Obstructive sleep apnea and abnormal cephalometric measurements. Implications for treatment. , 1984, Chest.

[80]  P. Trayhurn The development of obesity in animals: the role of genetic susceptibility. , 1984, Clinics in endocrinology and metabolism.

[81]  Y. Kawakami,et al.  Chemical and behavioral control of breathing in adult twins. , 1984, The American review of respiratory disease.

[82]  C. Guilleminault,et al.  Cephalometric analyses and flow-volume loops in obstructive sleep apnea patients. , 1983, Sleep.

[83]  M. Berman,et al.  Central role of high density lipoprotein in plasma free cholesterol metabolism. , 1982, The Journal of clinical investigation.

[84]  N. Cherniack,et al.  Respiratory dysrhythmias during sleep. , 1981, The New England journal of medicine.

[85]  M. Hallett,et al.  Obstructive sleep apnea in family members. , 1978, The New England journal of medicine.

[86]  R. A. Epstein,et al.  CONGENITAL FAILURE OF AUTOMATIC CONTROL OF VENTILATION, GASTROINTESTINAL MOTILITY AND HEART RATE , 1978 .

[87]  J. Weil,et al.  Hereditary aspects of decreased hypoxic response. , 1978, The Journal of clinical investigation.

[88]  J. Weil,et al.  Hypoventilation in obstructive lung disease. The role of familial factors. , 1978, The New England journal of medicine.

[89]  J. Weil,et al.  Respiratory failure associated with familial depression of ventilatory response to hypoxia and hypercapnia. , 1976, The New England journal of medicine.

[90]  C. Guilleminault,et al.  Sleep apnea in eight children. , 1976, Pediatrics.

[91]  S. Leeder,et al.  Ventilatory response to carbon dioxide in young athletes: a family study. , 1976, The American review of respiratory disease.

[92]  W. Nance,et al.  Multivariate analysis of craniofacial measurements in twin and family data. , 1974, American journal of physical anthropology.

[93]  D. Hudgel,et al.  Asthma associated with decreased hypoxic ventilatory drive. A family study. , 1974, Annals of internal medicine.

[94]  V. Beral,et al.  Insensitivity of respiratory centre to carbon dioxide in the Enga people of New Guinea. , 1971, Lancet.

[95]  R. Osborne,et al.  Genetic Basis of Morphological Variation: An Evaluation and Application of the Twin Study Method , 1962 .

[96]  N J Douglas,et al.  Neck and total body fat deposition in nonobese and obese patients with sleep apnea compared with that in control subjects. , 1998, American journal of respiratory and critical care medicine.

[97]  N. Schork,et al.  Ventilation and metabolism among rat strains. , 1997, Journal of applied physiology.

[98]  S. Saarelainen,et al.  Circulating endothelin-1 in obstructive sleep apnea. , 1997, Endothelium : journal of endothelial cell research.

[99]  S. Redline,et al.  Racial differences in sleep-disordered breathing in African-Americans and Caucasians. , 1997, American journal of respiratory and critical care medicine.

[100]  R. Kapur Contemporary approaches toward understanding the pathogenesis of Hirschsprung disease. , 1993, Pediatric pathology.

[101]  C. Bouchard,et al.  Genetic factors in obesity. , 1989, The Medical clinics of North America.

[102]  H. Kimura,et al.  Abnormal breathing during sleep and chemical control of breathing during wakefulness in patients with sleep apnea syndrome. , 1989, The American review of respiratory disease.

[103]  V. Tb Obesity, genetics, and ponderal set point. , 1988 .

[104]  T. Roth,et al.  Familial childhood sleep apnea. , 1988, Henry Ford Hospital medical journal.

[105]  D. Hudgel,et al.  The effects of weight and chemosensitivity on respiratory sleep abnormalities: a family study. , 1986, International journal of obesity.

[106]  T. Graber Nature versus nurture in dentofacial variation , 1985 .

[107]  A. Lundström Nature versus nurture in dento-facial variation , 1984 .

[108]  G. Bowes,et al.  The influence of sleep fragmentation on arousal and ventilatory responses to respiratory stimuli. , 1980, Sleep.

[109]  W C Dement,et al.  The sleep apnea syndromes. , 1976, Annual review of medicine.

[110]  V. Klissouras,et al.  Genetic differences in the ventilatory response to inhaled CO2. , 1974, Journal of applied physiology.