Obstructive Sleep Apnea Syndrome

Obstructive Sleep Apnea Syndrome

Observed genes

Polygenic score

Influential genes: SLC52A3, PACRG

A missense variant in the SLC52A3 gene was associated with Obstructive Sleep Apnea

A study identified an association of Obstructive Sleep Apnea with the PACRG gene.

Overview

Obstructive sleep apnea (OSA) is a condition in which individuals experience pauses in breathing during sleep. It is associated with a complete or partial closure of the airways. Patients often tend to snore and gasp as well. This influences the patient’s sleep and leads to fatigue and daytime sleepiness. It affects around 15% of adults and the prevalence is higher in men and increases with age.[1] Various genes are associated with this condition and are responsible for 40% of all cases.[2] Other risk factors include obesity, family history, some medications, smoking, alcohol, and other comorbidities. It can be diagnosed using various questionnaires or doing a sleep study (polysomnography). The treatment consists of lifestyle modifications and special devices that allow you to breathe normally during sleep.

Prevalence & Risk factors

The prevalence is estimated to be 15% of middle-aged adults.[1] It increases rapidly with age and is higher in men. Obesity is present in 70% of cases and is a major risk factor - fat deposits around the upper airway can constrict the airways making it difficult for patients to breathe, especially when asleep. Other risk factors include craniofacial and upper airway structural abnormalities, smoking, a family history of OSA, snoring, nasal congestion, some substances (like alcohol, benzodiazepines, opiates), and various health conditions (congestive heart failure, hypertension, Atrial fibrillation, pulmonary hypertension, end-stage kidney disease, chronic lung diseases like COPD, stroke, pregnancy, acromegaly, hypothyroidism, PCOS, Parkinson’s disease, etc.)

   

Genetics

OSA is a genetically complex disease that results from multiple interacting genetic and environmental factors.[2] Knowledge of the genetic background of OSA is quite behind compared to other common diseases. Obesity is known to be a major risk factor for OSA, which can be well managed. Meanwhile, studies of candidate genes focused on the relationship between selected single nucleotide polymorphisms (SNPs) and OSA phenotypes.

Despite the fact that the main risk factor is known as obesity, which is diagnosed in about 70% of OSA cases, it has been found that first-degree relatives of an OSA patient are at higher risk to snore or suffer from apneas. After taking into account obesity, age, and gender. One previously submitted genome-wide linkage analysis from the Cleveland Family study describes a connection between the ANGPT2 gene and mean nocturnal oxygen saturation, which indicates the severity of OSA.[3,4]

The LPAR1 gene is thought to be a potential susceptibility locus among African Americans, and PTGER3 gene polymorphism is likely to be associated with OSA among Europeans.[5] Furthermore, variations in 5-HTR2A (1438G/A) and 5-HTT genes might contribute to OSA as well, more specifically A allele of the 5-HTR2A polymorphism significantly increases the risk of OSA.[6]

It is important to mention that more studies and research is needed to deepen the knowledge of the genetic background of OSA. The majority of the studies struggled with small sample sets and cohorts, but the research is improving due to the technological progress in the field of next-generation sequencing. 

Genetic testing allows us to detect whether you have the predisposition to develop this disease. In Macromo, we use polygenic risk scores and causative evidence-based genetic variants for evaluation. The polygenic risk score (PRS) represents the total number of genetic variants that increase an individual's risk of developing a particular disease. All variants across their genome are summed and ranked according to their effect on disease development.

Signs & Symptoms

Most patients with OSA have a poor quality of sleep and complain of daytime sleepiness, morning headaches, or their bed partner reports loud snoring, gasping, choking, snorting, or interruptions in breathing while sleeping. This can lead to depression, decreased libido, impaired concentration, etc. Often people suffering from OSA are not aware of the problem, they don’t remember waking up. 

Diagnosis

The diagnosis is based on sleep history, questionnaires, and sleep studies (polysomnography). The primary measure that is used to establish the diagnosis is the apnea-hypopnea index (AHI). This is obtained from overnight polysomnography (PSG) and is a count of the number of episodes of breathing obstruction per hour of sleep. Polysomnography records your brain waves, the oxygen level in your blood, heart rate, and breathing, as well as eye and leg movements during the study. Male and female subjects are often considered to have OSA if the AHI exceeds a certain level, usually 5-10 events per hour.

Therapy

The treatment of choice is keeping the airways open by continuous positive airway pressure (CPAP) throughout the night. People use a special machine - it delivers air pressure through a piece that fits into your nose or is placed over your nose and mouth while you sleep. 

A Mouthpiece (oral device) can be used as an alternative. These are designed to keep your throat open during sleep. Otherwise, there are also some surgical procedures that could be performed to alleviate the symptoms. 

Prevention

It is possible to improve your symptoms and prevent the development of OSA through various lifestyle modifications. A lot of patients with OSA suffer from obesity and loss of weight can have a big influence (healthy diet and physical activity). Other preventive measures are cessation of smoking and alcohol intake (especially before bedtime), avoiding sedatives (like anti-anxiety or sleeping pills), and using a nasal decongestant or allergy medications if needed. Sleeping on the side or stomach can also lead to some improvements. 

Prognosis

OSA can lead to many serious complications. It is one of the most common causes of secondary hypertension. OSA also increases the risk of other cardiovascular conditions like coronary artery disease, heart attacks, heart failure, strokes, and abnormal heart rhythms (arrhythmias). The daytime sleepiness puts people at risk of work-related accidents and traffic accidents (falling asleep while driving). Other complications include eye problems (such as glaucoma and dry eyes), metabolic disorders (diabetes type 2), problems with pregnancy (gestational diabetes or low-birth-weight babies), and complications after surgery.

Recommendations

  • If you experience any symptoms, visit your doctor.
  • Improve your health through physical exercise, a healthy diet, and smoking cessation.
  • Don’t drink alcohol or take any sedative medications before bedtime.
  • Use a nasal decongestant or allergy pills if needed. 

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Recommendations

  • If you experience any symptoms, visit your doctor.
  • Improve your health through physical exercise, a healthy diet, and smoking cessation.
  • Don’t drink alcohol or take any sedative medications before bedtime.
  • Use a nasal decongestant or allergy pills if needed. 

Sources

  1. Kline L. R., (2021), Clinical presentation and diagnosis of obstructive sleep apnea in adults, UptoDate https://www-uptodate-com.ezproxy.is.cuni.cz/contents/clinical-presentation-and-diagnosis-of-obstructive-sleep-apnea-in-adults/abstract/4-6
  2. Redline, S., & Tishler, P. V. (2000). The genetics of sleep apnea. Sleep medicine reviews, 4(6), 583–602. https://doi.org/10.1053/smrv.2000.0120
  3. Wang H, Cade BE, Chen H, et al. Variants in angiopoietin-2 (ANGPT2) contribute to variation in nocturnal oxyhaemoglobin saturation level. Hum Mol Genet. říjen 2016:ddw324. doi:10.1093/hmg/ddw324
  4. Mukherjee S, Saxena R, Palmer LJ. The genetics of obstructive sleep apnoea. Respirology. 2017;23(1):18-27. doi:10.1111/resp.13212
  5. Patel SR, Goodloe R, De G, et al. Association of Genetic Loci with Sleep Apnea in European Americans and African-Americans: The Candidate Gene Association Resource (CARe). Esteban FJ, ed. PLoS ONE. 2012;7(11):e48836. doi:10.1371/journal.pone.0048836
  6. Xu H, Guan J, Yi H, Yin S. A Systematic Review and Meta-Analysis of the Association between Serotonergic Gene Polymorphisms and Obstructive Sleep Apnea Syndrome. Wang Y, ed. PLoS ONE. 2014;9(1):e86460. doi:10.1371/journal.pone.0086460
  7. Kline L. R., (2021), Clinical presentation and diagnosis of obstructive sleep apnea in adults, UptoDate https://www-uptodate-com.ezproxy.is.cuni.cz/contents/clinical-presentation-and-diagnosis-of-obstructive-sleep-apnea-in-adults/abstract/4-6
  8. Kreiger M. H., (2021), Management of obstructive sleep apnea in adults, UptoDate, https://www-uptodate-com.ezproxy.is.cuni.cz/contents/management-of-obstructive-sleep-apnea-in-adults?search=obstructive%20sleep%20apnea%20risk%20facotrs&source=search_result&selectedTitle=4~150&usage_type=default&display_rank=4#H19916919
  9. Obstructive sleep apnea - Symptoms and causes - Mayo Clinic https://www.mayoclinic.org/diseases-conditions/obstructive-sleep-apnea/symptoms-causes/syc-20352090
  10. Redline, S., & Tishler, P. V. (2000). The genetics of sleep apnea. Sleep medicine reviews, 4(6), 583–602. https://doi.org/10.1053/smrv.2000.0120

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