Dataset Information

Systems biology analyses of gene expression and genome wide association study data in obstructive sleep apnea.

ABSTRACT: 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.

SUBMITTER: Liu Y

PROVIDER: S-EPMC4465214 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature

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Systems biology analyses of gene expression and genome wide association study data in obstructive sleep apnea.

Liu Yu Y Patel Sanjay S Nibbe Rod R Maxwell Sean S Chowdhury Salim A SA Koyuturk Mehmet M Zhu Xiaofeng X Larkin Emma K EK Buxbaum Sarah G SG Punjabi Naresh M NM Gharib Sina A SA Redline Susan S Chance Mark R MR

Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing 20110101

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 ...[more]

PMID: 21121029

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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.

Project description:BackgroundWe hypothesized that obstructive sleep apnea (OSA) can predispose individuals to lower airway infections and community-acquired pneumonia (CAP) due to upper airway microaspiration. This study evaluated the association between OSA and CAP.MethodsWe performed a case-control study that included 82 patients with CAP and 41 patients with other infections (control group). The controls were matched according to age, sex and body mass index (BMI). A respiratory polygraph (RP) was performed upon admission for patients in both groups. The severity of pneumonia was assessed according to the Pneumonia Severity Index (PSI). The associations between CAP and the Epworth Sleepiness Scale (ESS), OSA, OSA severity and other sleep-related variables were evaluated using logistic regression models. The associations between OSA, OSA severity with CAP severity were evaluated with linear regression models and non-parametric tests.FindingsNo significant differences were found between CAP and control patients regarding anthropometric variables, toxic habits and risk factors for CAP. Patients with OSA, defined as individuals with an Apnea-Hypopnea Index (AHI) ≥10, showed an increased risk of CAP (OR = 2·86, 95%CI 1·29-6·44, p = 0·01). Patients with severe OSA (AHI≥30) also had a higher risk of CAP (OR = 3·18, 95%CI 1·11-11·56, p = 0·047). In addition, OSA severity, defined according to the AHI quartile, was also significantly associated with CAP (p = 0·007). Furthermore, OSA was significantly associated with CAP severity (p = 0·0002), and OSA severity was also associated with CAP severity (p = 0·0006).ConclusionsOSA and OSA severity are associated with CAP when compared to patients admitted to the hospital for non-respiratory infections. In addition, OSA and OSA severity are associated with CAP severity. These results support the potential role of OSA in the pathogenesis of CAP and could have clinical implications. This link between OSA and infection risk should be explored to investigate the relationships among gastroesophageal reflux, silent aspiration, laryngeal sensory dysfunction and CAP.Trial registrationClinicalTrials.gov NCT01071421.

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.

Project description:ImportanceObstructive sleep apnea (OSA) is more common among patients with asthma; whether asthma is associated with the development of OSA is unknown.ObjectiveTo examine the prospective relationship of asthma with incident OSA.Design, setting, and participantsPopulation-based prospective epidemiologic study (the Wisconsin Sleep Cohort Study) beginning in 1988. Adult participants were recruited from a random sample of Wisconsin state employees to attend overnight polysomnography studies at 4-year intervals. Asthma and covariate information were assessed during polysomnography studies through March 2013. Eligible participants were identified as free of OSA (apnea-hypopnea index [AHI] of <5 events/h and not treated) by 2 baseline polysomnography studies. There were 1105 4-year follow-up intervals provided by 547 participants (52% women; mean [SD] baseline age, 50 [8] years).ExposuresQuestionnaire-assessed presence and duration of self-reported physician-diagnosed asthma.Main outcomes and measuresThe associations of presence and duration of asthma with 4-year incidences of both OSA (AHI of ≥5 or positive airway pressure treatment) and OSA concomitant with habitual daytime sleepiness were estimated using repeated-measures Poisson regression, adjusting for confounders.ResultsTwenty-two of 81 participants (27% [95% CI, 17%-37%]) with asthma experienced incident OSA over their first observed 4-year follow-up interval compared with 75 of 466 participants (16% [95% CI, 13%-19%]) without asthma. Using all 4-year intervals, participants with asthma experienced 45 cases of incident OSA during 167 4-year intervals (27% [95% CI, 20%-34%]) and participants without asthma experienced 160 cases of incident OSA during 938 4-year intervals (17% [95% CI, 15%-19%]); the corresponding adjusted relative risk (RR) was 1.39 (95% CI, 1.06-1.82), controlling for sex, age, baseline and change in body mass index, and other factors. Asthma was also associated with new-onset OSA with habitual sleepiness (RR, 2.72 [95% CI, 1.26-5.89], P = .045). Asthma duration was related to both incident OSA (RR, 1.07 per 5-year increment in asthma duration [95% CI, 1.02-1.13], P = .01) and incident OSA with habitual sleepiness (RR, 1.18 [95% CI, 1.07-1.31], P = .02).Conclusions and relevanceAsthma was associated with an increased risk of new-onset OSA. Studies investigating the mechanisms underlying this association and the value of periodic OSA evaluation in patients with asthma are warranted.

Dataset Information

Systems biology analyses of gene expression and genome wide association study data in obstructive sleep apnea.

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Systems biology analyses of gene expression and genome wide association study data in obstructive sleep apnea.

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