Empirical assessment of allele frequencies of genome wide association study variants associated with obstructive sleep apnea.
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ABSTRACT: Objective
Obstructive Sleep Apnea (OSA) is a heterogeneous disorder with a complex interplay of genetic and environmental factors. Over the years, with advancement in genotyping and sequencing techniques, various loci have shown an association with OSA. It is pertinent to understand the status of these associated variants in different ethnic groups. The aim of the study was to assess the genetic affinity among different population groups by evaluating the risk allele frequencies of variants associated with OSA.Method
The variants associated with OSA were obtained from the GWAS catalog with a significant p value of <5 × 10-7; 95 variants were obtained (www.ebi.ac.uk/gwas). Further, the variants were narrowed down on the basis of risk allele frequencies (>5%). The fst was calculated to assess the genetic affinity between super population groups and among the sub-population groups present in the 1000 genome project.Result
The fst values observed indicated all super populations were genetically related (SAS, AMR, EAS and EUR) except in the African (AFR) population group. Further, the closely related super population i.e., SAS, AMR, EAS and EUR when bifurcated on the basis of sub-population groups shows population stratification and SAS population groups form separate clusters on the MDS plot.Conclusion
The study highlights genetic heterogeneity among different population groups that gets diluted and results are biased when the samples are pooled irrespective of their endogamous groups. Our results provide insight to researchers to target specific endogamous groups for future studies on OSA.
SUBMITTER: Mohit
PROVIDER: S-EPMC9185076 | biostudies-literature | 2022
REPOSITORIES: biostudies-literature
Publications
Empirical assessment of allele frequencies of genome wide association study variants associated with obstructive sleep apnea.
Mohit Sharma Indu I Sharma Varun V Kumar Sachin S Rastogi Garima G Dutt Pranjali P Shrivastava Ashutosh A Rai Niraj N Chand Pooran P
American journal of translational research 20220515 5
<h4>Objective</h4>Obstructive Sleep Apnea (OSA) is a heterogeneous disorder with a complex interplay of genetic and environmental factors. Over the years, with advancement in genotyping and sequencing techniques, various loci have shown an association with OSA. It is pertinent to understand the status of these associated variants in different ethnic groups. The aim of the study was to assess the genetic affinity among different population groups by evaluating the risk allele frequencies of varia ...[more]
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Project description:Rationale: Obstructive sleep apnea (OSA) has been associated with metabolic dysregulation and systemic inflammation. This may be due to pathophysiologic effects of OSA on visceral adipose tissue. We sought to assess the transcriptional consequences of OSA on adipocytes by utilizing pathway-focused analyses. Methods: Patients scheduled to undergo ventral hernia repair surgery were recruited to wear a portable home sleep monitor for two nights prior to surgery. Visceral fat biopsies were obtained intra-operatively. RNA was extracted and whole-genome expression profiling was performed. Gene Set Enrichment Analysis (GSEA) was used to identify curated gene sets that were differentially enriched in OSA subjects. Network analysis was applied to a select set of highly enriched pathways. Results: 10 patients with OSA and 8 control subjects were recruited. There were no differences in age, gender, body mass index between the two groups, but the OSA subjects had a significantly higher respiratory disturbance index (19.2 vs. 0.6, P-value 0.05) and worse hypoxemia (minimum oxygen saturation 79.7% vs. 87.8%, P-value < 0.001). GSEA identified a number of gene sets up-regulated in adipose tissue of OSA patients including the pro-inflammatory NF-M-NM-:B pathway and the proteolytic ubiquitin/proteasome module. A critical metabolic pathway, the peroxisome proliferator-activated receptor (PPAR), was down-regulated in subjects with OSA. Network analysis linked members of these modules together and identified regulatory hubs. Conclusions: OSA is associated with alterations in visceral fat gene expression. Pathway-based network analysis highlighted perturbations in several key pathways whose coordinated interactions may contribute to the metabolic dysregulation observed in this complex disorder. Total RNA from visceral fat of 18 subjects (10 OSA, 8 Control) was hybridized to 18 Affymetrix Genechip Human Gene 1.0 ST microarrays.
2012-09-01 | E-GEOD-38792 | biostudies-arrayexpress
Project description:Importance:While much has been reported on the relationship between floppy eyelid syndrome and obstructive sleep apnea (OSA), the diagnostic criteria of floppy eyelid syndrome are often subjective and vague. Objective:To evaluate the association between OSA and quantitative markers of eyelid laxity or secondary ocular surface disease in a sleep clinic population. Design, Setting, and Participants:This investigation was a cross-sectional observational study at the Center for Sleep Medicine at Icahn School of Medicine at Mount Sinai. Participants were individuals referred for overnight polysomnography from March 1 to August 30, 2015. Main Outcomes and Measures:Eyelid laxity and ocular surface disease were assessed on bedside ophthalmologic examination. The presence and severity of OSA were determined from polysomnography results. Initial correlation between OSA and ocular surface and eyelid markers was calculated through bivariate linear regression analysis, and the association between ocular symptoms was obtained through bivariate ordered logistic regression. Analysis was repeated adjusting for known associations between OSA and sex, age, body mass index, and medical comorbidities through multivariable analysis. Results:In total, 201 individuals (402 eyes) were enrolled in the study. Their mean (SD) age was 53.2 (13.5) years, 43.3% (n?=?87) were female, 56.7% (n?=?114) were of white race/ethnicity, 26.9% (n?=?54) were black/African American, 4.0% (n?=?8) were Asian, 8.0% (n?=?16) were multiracial or other, and 4.5% (n?=?9) were of unknown race/ethnicity, with 21.9% (n?=?44) of all individuals self-identifying as Hispanic and 75.1% (n?=?151) self-identifying as non-Hispanic. After adjustment, no association was observed between OSA severity and an eyelid laxity score (regression coefficient, 0.85; 95% CI, -0.33 to 0.62; P?=?.40) or an ocular surface score (regression coefficient, 1.09; 95% CI, -0.32 to 0.29; P?=?.93). Through subset analysis, male sex was associated with a higher ocular surface score, while older age and diabetes were associated with a higher eyelid laxity score. Only one patient (0.5%) exhibited findings of floppy eyelid syndrome. Conclusions and Relevance:Among individuals referred for overnight polysomnography, quantitative markers of eyelid laxity were not associated with the presence or severity of OSA. Subset analysis suggests that prior studies may have been limited by confounding variables or the technique of identifying eyelid laxity.
| S-EPMC5710483 | biostudies-other
Project description:Rationale: Obstructive sleep apnea (OSA) has been associated with metabolic dysregulation and systemic inflammation. This may be due to pathophysiologic effects of OSA on visceral adipose tissue. We sought to assess the transcriptional consequences of OSA on adipocytes by utilizing pathway-focused analyses. Methods: Patients scheduled to undergo ventral hernia repair surgery were recruited to wear a portable home sleep monitor for two nights prior to surgery. Visceral fat biopsies were obtained intra-operatively. RNA was extracted and whole-genome expression profiling was performed. Gene Set Enrichment Analysis (GSEA) was used to identify curated gene sets that were differentially enriched in OSA subjects. Network analysis was applied to a select set of highly enriched pathways. Results: 10 patients with OSA and 8 control subjects were recruited. There were no differences in age, gender, body mass index between the two groups, but the OSA subjects had a significantly higher respiratory disturbance index (19.2 vs. 0.6, P-value 0.05) and worse hypoxemia (minimum oxygen saturation 79.7% vs. 87.8%, P-value < 0.001). GSEA identified a number of gene sets up-regulated in adipose tissue of OSA patients including the pro-inflammatory NF-κB pathway and the proteolytic ubiquitin/proteasome module. A critical metabolic pathway, the peroxisome proliferator-activated receptor (PPAR), was down-regulated in subjects with OSA. Network analysis linked members of these modules together and identified regulatory hubs. Conclusions: OSA is associated with alterations in visceral fat gene expression. Pathway-based network analysis highlighted perturbations in several key pathways whose coordinated interactions may contribute to the metabolic dysregulation observed in this complex disorder.
2012-09-01 | GSE38792 | GEO
Project description:Study objectivesObstructive sleep apnea (OSA) increases the risk of cognitive impairment. Measures of sleep microarchitecture from EEG may help identify patients at risk of this complication.MethodsParticipants with suspected OSA (n = 1142) underwent in-laboratory polysomnography and completed sleep and medical history questionnaires, and tests of global cognition (Montreal Cognitive Assessment, MoCA), memory (Rey Auditory Verbal Learning Test, RAVLT) and information processing speed (Digit-Symbol Coding, DSC). Associations between cognitive scores and stage 2 non-rapid eye movement (NREM) sleep spindle density, power, frequency and %-fast (12-16Hz), odds-ratio product (ORP), normalized EEG power (EEGNP), and the delta:alpha ratio were assessed using multivariable linear regression (MLR) adjusted for age, sex, education, and total sleep time. Mediation analyses were performed to determine if sleep microarchitecture indices mediate the negative effect of OSA on cognition.ResultsAll spindle characteristics were lower in participants with moderate and severe OSA (p ≤ .001, vs. no/mild OSA) and positively associated with MoCA, RAVLT, and DSC scores (false discovery rate corrected p-value, q ≤ 0.026), except spindle power which was not associated with RAVLT (q = 0.185). ORP during NREM sleep (ORPNREM) was highest in severe OSA participants (p ≤ .001) but neither ORPNREM (q ≥ 0.230) nor the delta:alpha ratio were associated with cognitive scores in MLR analyses (q ≥ 0.166). In mediation analyses, spindle density and EEGNP (p ≥ .048) mediated moderate-to-severe OSA's negative effect on MoCA scores while ORPNREM, spindle power, and %-fast spindles mediated OSA's negative effect on DSC scores (p ≤ .018).ConclusionsAltered spindle activity, ORP and normalized EEG power may be important contributors to cognitive deficits in patients with OSA.
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Project description:Study objectivesThe objective of the study is to validate the performance of Belun Ring Platform, a novel home sleep apnea testing system using a patented pulse oximeter sensor and a proprietary cloud-based neural networks algorithm.MethodsThe Belun Ring captures oxygen saturation, photoplethysmography, and accelerometer signals. The Belun Ring total sleep time is derived from features extracted from accelerometer, oxygen saturation, and photoplethysmography signals. The Belun Ring respiratory event index is derived from Belun Ring total sleep time and features extracted from heart rate variability and oxygen saturation changes. A total of 50 adults without significant cardiopulmonary or neuromuscular comorbidities and heart rate affecting medications were evaluated. In-lab sleep studies were performed simultaneously with the Ring and the studies were manually scored using the American Academy of Sleep Medicine Scoring Manual 4% desaturation criteria.ResultsThe Belun Ring respiratory event index correlated well with the polysomnography-apnea-hypopnea index (AHI; r = .894, P < .001). The sensitivity and specificity in categorizing AHI ≥ 15 events/h were 0.85 and 0.87, respectively, and the positive predictive value and negative predictive value were 0.88 and 0.83, respectively. The Belun Ring total sleep time also correlated well with the polysomnography-total sleep time (r = .945, P < .001). Although the Belun Ring Platform has a good overall performance, it tends to overestimate AHI in individuals with AHI under 15 events/h and underestimate AHI in those with AHI over 15 events/h. Conclusions: In this proof-of-concept study, the Belun Ring Platform demonstrated a reasonable accuracy in predicting AHI and total sleep time in patients without significant comorbidities and heart rate-affecting medications.Clinical trial registrationRegistry: ClinicalTrials.gov; Name: Validation of a Novel Device for Screening Patients With Symptoms of Obstructive Sleep Apnea; URL: https://clinicaltrials.gov/ct2/show/NCT04121923; Identifier: NCT04121923.
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Project description:The precise molecular etiology of obstructive sleep apnea (OSA) is unknown; however recent research indicates that several interconnected aberrant pathways and molecular abnormalities are contributors to OSA. Identifying the genes and pathways associated with OSA can help to expand our understanding of the risk factors for the disease as well as provide new avenues for potential treatment. Towards these goals, we have integrated relevant high dimensional data from various sources, such as genome-wide expression data (microarray), protein-protein interaction (PPI) data and results from genome-wide association studies (GWAS) in order to define sub-network elements that connect some of the known pathways related to the disease as well as define novel regulatory modules related to OSA. Two distinct approaches are applied to identify sub-networks significantly associated with OSA. In the first case we used a biased approach based on sixty genes/proteins with known associations with sleep disorders and/or metabolic disease to seed a search using commercial software to discover networks associated with disease followed by information theoretic (mutual information) scoring of the sub-networks. In the second case we used an unbiased approach and generated an interactome constructed from publicly available gene expression profiles and PPI databases, followed by scoring of the network with p-values from GWAS data derived from OSA patients to uncover sub-networks significant for the disease phenotype. A comparison of the approaches reveals a number of proteins that have been previously known to be associated with OSA or sleep. In addition, our results indicate a novel association of Phosphoinositide 3-kinase, the STAT family of proteins and its related pathways with OSA.
| S-EPMC4465214 | biostudies-literature
Project description:BackgroundObstructive sleep apnea frequently persists in children following adenotonsillectomy, which is the first-line treatment recommended for obstructive sleep apnea with adenotonsillar hypertrophy. Drug-induced sleep endoscopy (DISE) is a diagnostic tool increasingly used to assess pediatric obstructive sleep apnea, but its use has not been standardized. The overarching goal of this study was to document the current practice of Canadian otolaryngologists managing this population.MethodsA nation-wide online cross-sectional survey of Canadian otolaryngologist members of the Canadian Society of Otolaryngology - Head and Neck Surgery and the Association d'otorhinolaryngologie et chirurgie cervico-faciale du Québec. The 58-question electronic survey was developed based on a validated survey redaction guide with the aim to assess management and treatment of pediatric obstructive sleep apnea, as well as indications and performance of DISE. Consensus on practice items was defined by a minimum of 75% similar answers.ResultsOne hundred and nine Canadian otolaryngologists completed the survey on management of pediatric obstructive sleep apnea, among which 12 of them completed the questions on DISE. Overall, there was a poor rate of agreement of 55% among the respondents for the 58 questions altogether. There was a consensus to assess pediatric obstructive sleep apnea clinically ± with videos (82.6%), to assess adenotonsillar hypertrophy clinically (93.6%) and with flexible scope in the office (80.7%), as well as for the airway sites examined endoscopically during DISE. However, there was no consensus regarding anesthetic protocol and scoring system. DISE was mostly performed in cases of persistent obstructive sleep apnea after adenotonsillectomy rather than before performing any surgical procedure. There was no difference in the management of obstructive sleep apnea between otolaryngologists who perform DISE and those who do not. The only difference between otolaryngologists who practice in community centers versus in tertiary care centers was the more frequently use of the Brodsky tonsil scale by the latter ones.ConclusionThis Canadian-wide survey highlighted a lack of consensus in the management of pediatric obstructive sleep apnea and DISE. Certain aspects regarding DISE remain unclear, including establishment of its ideal timing in order to eventually avoid unnecessary tonsillectomies.
| S-EPMC8408936 | biostudies-literature
Project description:BackgroundObstructive sleep apnea syndrome (OSAS) and laryngopharyngeal reflux (LPR) have been found to coexist in the population. OSAS and LPR also share obesity as an important risk factor. However, the relationship between LPR and OSAS remains unclear. This study aimed to correlate LPR as measured by the Reflux Symptom Index (RSI) and the Reflux Finding Score (RFS) with OSAS.MethodsThis cross-sectional study included sixty-four subjects who underwent anamnesis to complete the RSI and the Epworth Sleeping Scale (ESS). The subjects were then divided into the OSAS and non-OSAS groups based on the Apnea-Hypopnea Index (AHI) obtained through a polysomnography examination. Both groups underwent a flexible fiberoptic nasopharyngolaryngoscopy examination to determine the RFS. LPR was identified based on the RSI and RFS.ResultsThe mean BMI of the OSAS group significantly was higher than the non-OSAS group (p < 0.05). Most of the subjects in the OSAS group exhibited mild-moderate OSAS (AHI 10-29), and severe OSAS occurred in only seven subjects. The mean RSI and RFS values in the OSAS group did not differ significantly from the non-OSAS group (p = 0.34 and p = 0.36, respectively). The proportion of LPR between the mild-moderate OSAS group, the severe OSAS group, and the non-OSAS group did not differ significantly (p = 1.00). RSI and RFS did not significantly correlate with AHI. Based on RSI, the proportion of LPR between the ESS (+) and ESS (-) groups did not significantly differ (adjusted p = 0.062). The proportion of LPR based on RFS was almost equal between the ESS (+) and ESS (-) groups (p = 0.817).ConclusionsThe BMI of the OSAS group was significantly higher than the non-OSAS group. There was no significant difference in RSI and RFS between the OSAS and non-OSAS groups. There was no significant correlation between RSI and AHI, or between RFS and AHI. There was no significant difference in the proportion of RSI between the ESS (+) and the ESS (-) groups.
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Project description:This study evaluates the relationship between obstructive sleep apnea (OSA) and asthma. Literature search was carried out in several electronic databases and random effects meta-analyses were performed to obtain pooled estimates of the prevalence of OSA, OSA risk and sleep disordered breathing (SDB) in asthma patients and pooled odds ratios of the prevalence between asthma and non-asthma patients. In adult asthma patients, the prevalence [95% confidence interval] of OSA, OSA risk, and SDB was 49.50 [36.39, 62.60] %, 27.50 [19.31, 35.69] %, and 19.65 [14.84, 24.46] % respectively. The odds of having OSA, OS risk and SDB by the asthma patients were 2.64 [1.76, 3.52], 3.73 [2.90, 4.57] and 1.73 [1.11, 2.36] times higher (p < 0.00001 for all) in asthma than in non-asthma patients, respectively. Adult asthma patients with OSA had significantly higher BMI in comparison with asthma patients without OSA. This study reveals that the prevalence of OSA in asthma patients is considerably higher; even higher than OSA risk and SDB. Sleep studies should be performed in asthma patients with symptoms suggestive of OSA/OSA risk/SDB.
| S-EPMC5481327 | biostudies-literature