Association of obstructive sleep apnea syndrome with polycystic ovary syndrome through bidirectional Mendelian randomization
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SUBMITTER: Liu P
PROVIDER: S-EPMC11239387 | biostudies-literature | 2024 Jan
REPOSITORIES: biostudies-literature
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Project description:BackgroundPrevious studies have reported associations between obstructive sleep apnea (OSA) and several mental disorders. However, further research is required to determine whether these associations are causal. Therefore, we evaluated the bidirectional causality between the genetic liability for OSA and nine mental disorders by using Mendelian randomization (MR).MethodWe performed two-sample bidirectional MR of genetic variants for OSA and nine mental disorders. Summary statistics on OSA and the nine mental disorders were extracted from the FinnGen study and the Psychiatric Genomics Consortium. The primary analytical approach for estimating causal effects was the inverse-variance weighted (IVW), with the weighted median and MR Egger as complementary methods. The MR Egger intercept test, Cochran's Q test, Rucker's Q test, and the MR pleiotropy residual sum and outlier (MR-PRESSO) test were used for sensitivity analyses.ResultMR analyses showed that genetic liability for major depressive disorder (MDD) was associated with an increased risk of OSA (odds ratio [OR] per unit increase in the risk of MDD, 1.29; 95% CI, 1.11-1.49; P < 0.001). In addition, genetic liability for OSA may be associated with an increased risk of attention-deficit/hyperactivity disorder (ADHD) (OR = 1.26; 95% CI, 1.02-1.56; p = 0.032). There was no evidence that OSA is associated with other mental disorders.ConclusionOur study indicated that genetic liability for MDD is associated with an increased risk of OSA without a bidirectional relationship. Additionally, there was suggestive evidence that genetic liability for OSA may have a causal effect on ADHD. These findings have implications for prevention and intervention strategies targeting OSA and ADHD. Further research is needed to investigate the biological mechanisms underlying our findings and the relationship between OSA and other mental disorders.
| S-EPMC11040841 | biostudies-literature
Project description:BackgroundObservational studies have reported associations between Barrett's esophagus (BE) and obstructive sleep apnea syndrome (OSAS), but the causal relationship remained unclear due to potential confounding biases. Our study aimed to elucidate this causal relationship by deploying a two-sample Mendelian randomization (MR) methodology.MethodsInstrumental variables (IVs) for Barrett's esophagus were obtained from a public database that comprised 13,358 cases and 43,071 controls. To investigate OSAS, we utilized summary statistics from a comprehensive genome-wide association study (GWAS) encompassing 38,998 cases of OSAS and 336,659 controls. Our MR analyses adopted multiple techniques, including inverse variance weighted (IVW), weighted median, weighted mode, MR-Egger, and simple mode.ResultsThe IVW analysis established a causal relationship between Barrett's esophagus and OSAS, with an odds ratio (OR) of 1.19 and a 95% confidence interval (CI) of 1.11-1.28 (p = 8.88E-07). Furthermore, OSAS was identified as a contributing factor to the onset of Barrett's esophagus, with an OR of 1.44 and a 95% CI of 1.33-1.57 (p = 7.74E-19). Notably, the MR-Egger intercept test found no evidence of directional pleiotropy (p > 0.05).ConclusionThis study identifies a potential association between BE and an increased occurrence of OSAS, as well as the reverse relationship. These insights could influence future screening protocols and prevention strategies for both conditions.
| S-EPMC10796615 | biostudies-literature
Project description:BackgroundObstructive sleep apnea-hypopnea syndrome (OSAHS) is correlated with metabolic deterioration in patients experiencing polycystic ovary syndrome (PCOS). Women diagnosed with PCOS exhibit a heightened prevalence of OSAHS. This meta-analysis aims to assess the morbidity of OSAHS in women affected by PCOS and to examine the differences in metabolism-related indicators between OSAHS-positive and OSAHS-negative in women with PCOS.MethodsA comprehensive literature analysis of OSAHS morbidity in women with PCOS was conducted, utilizing databases such as CNKI, EMBASE, PubMed, Web of Science, and Wanfang. A comparison was carried out between patients with OSAHS-positive and those with OSAHS-negative in terms of their clinical characteristics and metabolic differences. The search language included English and Chinese. The acquired data were analyzed by employing RevMan 5.2 and Stata 11.0. Continuous variables with the same units were combined and analyzed through weighted mean differences (WMDs) as effect sizes, while continuous variables with different units were combined and analyzed through standardized mean differences (SMDs) as effect sizes. A conjoint analysis was performed on the basis of I2 value, using either a fixed effect model (I2 ≤ 50%) or a random effect model (I2 > 50%).ResultsA total of 21 articles met the inclusion criteria for this study. The findings indicated that 20.8% of women with PCOS were found to have comorbid OSAHS. The subjects were categorized into various subgroups for meta-analysis on the basis of race, age, disease severity, body mass index (BMI), and diagnostic criteria of PCOS. The results revealed high morbidity of OSAHS in all subgroups. In addition, most metabolic indicators and parameters of metabolic syndrome were notably worse in women suffering from both PCOS and OSAHS in comparison to their counterparts solely diagnosed with PCOS.ConclusionThe current literature indicates higher morbidity of OSAHS among women with PCOS, linking OSAHS with worse metabolic status and obesity in this population. Consequently, clinicians are advised to prioritize the detection and management of OSAHS in women with PCOS.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/#myprospero PROSPERO, identifier (CRD42024528264).
| S-EPMC11377251 | biostudies-literature
Project description:BackgroundObservational studies have suggested that obstructive sleep apnea (OSA) is in relation to atrial fibrillation (AF); however, these studies might be confounded and whether the relationship is causal remains unclear. We conducted a bidirectional Mendelian randomization (MR) study to clarify the causal inference between OSA and AF.MethodsGenetic instruments for OSA and AF were obtained from genome-wide association studies. The fixed-effects inverse-variance weighted (IVW) method was used as the main method, supplemented by several sensitivity analyses. For replication, another AF dataset was used to validate the causal effect of OSA on AF. Furthermore, multivariable MR analyses were performed to obtain direct estimates adjusting for potential confounders.ResultsGenetic liability to OSA was found to be significantly associated with a higher AF risk in the fixed-effects IVW method [odds ratio (OR) 1.210; 95% CI 1.119-1.307; P = 1.51 × 10-6]. The results were consistent in MR sensitivity analyses as well as in replication analyses, and the significance remained after adjusting for potential confounders. In the reverse MR analyses, there was no causal effect of AF on OSA.ConclusionsOur study strengthened the causal evidence of genetically predicted OSA with a higher AF risk. Early screening and appropriate management of OSA might show anti-arrhythmic benefits.
| S-EPMC8851818 | biostudies-literature
Project description:BackgroundsThe COVID-19 pandemic has caused significant impact on human health. Whether obstructive sleep apnea (OSA) increases the risk of COVID-19 remains unclear. We sought to clarify this issue using two-sample Mendelian randomization (TSMR) analysis in large cohorts.MethodsBidirectional two-sample Mendelian randomization (MR) was used to evaluate the potential causality between OSA and COVID-19 by selecting single-nucleotide polymorphisms (SNPs) as instrumental variables (IVs) from genome-wide association studies (GWAS). The inverse-variance weighted (IVW) method was selected as the main approach for data analysis to estimate the possible causal effects. Alternative methods such as MR-Egger, the MR pleiotropy residual sum and outlier (MR-PRESSO), and leave-one-out analysis methods were implemented as sensitivity analysis approaches to ensure the robustness of the results.ResultsAll forward MR analyses consistently indicated the absence of a causal relationship between OSA and any COVID-19 phenotype. In the reverse MR analysis, the IVW mode demonstrated that severe respiratory confirmed COVID-19 was correlated with a 4.9% higher risk of OSA (OR, 1.049; 95%CI, 1.018-1.081; P = 0.002), consistent in MR-PRESSO (OR = 1.049, 95%CI 1.018-1.081, P = 0.004), weighted median (OR = 1.048, 95%CI 1.003-1.095, P = 0.035), and MR-Egger (OR = 1.083, 95%CI 1.012-1.190, P = 0.041) methods.ConclusionsThere is no significant evidence supporting a causal association between OSA and any COVID phenotype, while we identified potential evidence for a causal effect of severe COVID-19 on an increased risk of OSA.
| S-EPMC9557138 | biostudies-literature
Project description:BackgroundSeveral studies have documented the high prevalence of obstructive sleep apnea (OSA) among women with polycystic ovary syndrome (PCOS). However, causal relationships between the two conditions remain unconfirmed. This study aims to assess the causal relationships between OSA and PCOS.MethodsWe conducted a two-sample Mendelian randomization (MR) analysis utilizing instrumental variables (IVs) derived from large-scale genome-wide association studies (GWAS) to genetically estimate the causal effects of PCOS on OSA. To explore the impact of PCOS on OSA across different ethnicities, we analyzed GWAS data from European and East Asian participants. The inverse variance weighted (IVW) method was the primary statistical approach. A series of sensitivity analyses, including the weighted median, MR-Egger, weighted mode methods, and leave-one-out analysis, were performed to evaluate the robustness of our MR results.ResultsIn the IVW analysis, the odds ratio (OR) for the association between PCOS and OSA was 1.133 [95% confidence interval (CI): 1.037-1.239, P=0.006], indicating that PCOS significantly increases the risk of OSA in the European population. No evidence of heterogeneity or directional pleiotropy was found using Cochran's Q test and the MR-Egger test. Conversely, the IVW analysis did not reveal a causal effect of PCOS on OSA in the East Asian population (OR =1.061, 95% CI: 0.888-1.268, P=0.51).ConclusionsOur findings suggest that European women with PCOS are at an increased risk for OSA. However, no association was observed between PCOS and OSA in the East Asian population. Clinicians should maintain a high index of suspicion for OSA in women with PCOS, particularly among the European demographic.
| S-EPMC11635232 | biostudies-literature
Project description:Polycystic ovary syndrome (PCOS) is defined as a chronic low-grade inflammatory reproductive endocrine disorder. PCOS can induce various metabolic disorders, which are associated with a state of mild and slow-acting inflammation. Nevertheless, the causal relationship between polycystic ovary syndrome and inflammatory factors is uncertain. The causality between inflammatory cytokines and PCOS was analyzed by bidirectional Mendelian randomization (MR) in this current probe. We performed an interactive MR study to assess the causal relationships between 91 inflammatory cytokines and PCOS using Genome Wide Association Study (GWAS) data. We underwent dual-sample MR analysis with inverse variance weights (IVW) as the predominant MR methodology with multiple validity and heterogeneity analyses. MR-Egger, weighted median, simple mode, weighted mode and MR-PRESSO were analyzed as multiple likelihood sensitivity analyses to enhance the final results.The results came out interleukin-1-alpha (IL-1 A) levels (odds ratio [OR] = 1.051, 95% fiducial interval [95% CI] = 1.009-1.095, P = 0.02) and oncostatin-M (OSM) levels ( [OR] = 1.041, [95% CI] = 1.001-1.082, P = 0.04) were positively associated with the development of PCOS. Moreover, interleukin-7 (IL-7) levels ([OR] = 0.935, [95% CI] = 0.884-0.989, P = 0.02); interleukin-15 receptor subunit alpha (IL15RA) levels ([OR] = 0.959, [95% CI] = 0.929-0.99, P = 0.01); and C-X-C motif chemokine 11 (CXCL11) levels ([OR] = 0.959, [95% CI] = 0.922-0.996. P = 0.03) were strongly negatively associated with PCOS. However, we did not find any strong positive results in the reverse analysis, suggesting that although inflammatory factors contribute to the pathogenesis of PCOS, PCOS itself does not trigger inflammatory factor production.Our study provides genetic evidence for the connection between systemic inflammatory regulators and PCOS. Treatments targeting specific inflammatory factors may help to mitigate the risk of PCOS. The levels of five of the 91 inflammatory factors included in this study, namely, IL1A and OSM, were associated with PCOS. IL1A and OSM contribute to the progression of PCOS while IL-7, IL15RA, and CXCL11 levels are negatively correlated with the development of PCOS.
| S-EPMC11539607 | biostudies-literature
Project description:BackgroundAccumulating observational studies have indicated that vitamin D deficiency (serum 25-hydroxyvitamin D (25OHD) < 50 nmol/L) is common in women with polycystic ovary syndrome (PCOS). However, the direction and causal nature remain unclear. In this study, we aimed to investigate the causal association between PCOS and 25OHD.MethodsA bidirectional two-sample Mendelian randomization (MR) study was used to evaluate the causal association between PCOS and 25OHD. From the publicly available European-lineage genome-wide association studies (GWAS) summary statistics for PCOS (4,890 cases of PCOS and 20,405 controls) and 25OHD (n = 417,580), we selected 11 and 102 single nucleotide polymorphisms (SNPs) as instrumental variables (IVs), respectively. In univariate MR (uvMR) analysis, inverse-variance weighted (IVW) method was employed in the primary MR analysis and multiple sensitivity analyses were implemented. Additionally, a multivariable MR (mvMR) design was carried to adjust for obesity and insulin resistance (IR) as well.ResultsUvMR demonstrated that genetically determined PCOS was negatively associated with 25OHD level (IVW Beta: -0.02, P = 0.008). However, mvMR found the causal effect disappeared when adjusting the influence of obesity and IR. Both uvMR and mvMR analysis didn't support the causal effect of 25OHD deficiency on risk of PCOS (IVW OR: 0.86, 95% CI: 0.66 ~ 1.12, P = 0.280).ConclusionOur findings highlighted that the casual effect of PCOS on 25OHD deficiency might be mediated by obesity and IR, and failed to find substantial causal effect of 25OHD deficiency on risk of PCOS. Further observational studies and clinical trials are necessary.
| S-EPMC10034407 | biostudies-literature
Project description:BackgroundExtensive observational evidence suggests an association between psychiatric disorders (PDs) and obstructive sleep apnea (OSA), but their causal relationship remains unexplored. The objective of this study was to examine the causal relationship between PDs and OSA.MethodsMendelian randomization (MR) analysis was conducted with summary genetic data from the FinnGen and Psychiatric Genomics Consortium (PGC). Inverse-variance weighted (IVW), MR-Egger, weighted median, and weighted mode methods were employed to ascertain causal influence. Sensitivity analysis employing various methodologies assessed the robustness of the findings. Furthermore, multivariable Mendelian randomization (MVMR) was used to clarify if the exposures independently caused OSA.ResultsMR analysis showed that genetically determined major depressive disorder (MDD) increased the risk of OSA (IVW odds ratio [OR]: 1.377, 95% confidence interval [CI]: 1.242-1.526, P = 1.05×10-9). Sensitivity analysis showed no evidence of pleiotropy and heterogeneity. In MVMR, the significant association persisted after adjusting for BMI, smoking, and alcohol consumption. No conclusive evidence indicated the causal impact of other psychological characteristics on OSA. In the reverse MR analyses, there was no causal effect of OSA on PDs.ConclusionThis study suggests a causal effect of MDD on OSA risk. Further research is needed to confirm these findings and understand how MDD contributes to OSA development, potentially aiding in reducing OSA incidence.
| S-EPMC10903261 | biostudies-literature
Project description:Although previous epidemiological studies have investigated the correlation between hypothyroidism and obstructive sleep apnea (OSA), the results are controversial and conflicting. Therefore, we used a bidirectional 2-sample Mendelian randomization (MR) approach to infer the causal relationship between hypothyroidism and OSA. We performed a bidirectional 2-sample MR analysis to infer the causal relationship between hypothyroidism and OSA using genome-wide association study (GWAS) data. The hypothyroidism dataset was obtained from GWAS of the IEU database (https://gwas.mrcieu.ac.uk/). The GWAS dataset associated with OSA was obtained from the FinnGen Biobank (https://www.finngen.fi/en). MR results were estimated using the inverse variance weighted, weighted median, MR-Egger, simple mode, and weighted mode methods. Sensitivity analysis was conducted using the heterogeneity, pleiotropy, and leave-one-out tests. Scatter plots, forest plots, funnel plots, and leave-one-out plots were used as visualizations of MR results. According to the inverse variance weighted method, forward MR analysis showed that hypothyroidism was significantly associated with OSA (odds ratio, 1.870 [95% confidence interval, 1.055-3.315]; P = .032). There was no evidence to suggest a causal relationship between OSA and the risk of hypothyroidism in reverse MR analysis (P = .881). Furthermore, sensitivity analysis further confirmed the robust results. Our bidirectional 2-sample MR analysis revealed that hypothyroidism could increase the risk of developing OSA but did not provide evidence to support a causal relationship of OSA on hypothyroidism. Thus, patients with hypothyroidism should strengthen their sleep quality monitoring, and further research is needed to understand the role of hypothyroidism effects on OSA.
| S-EPMC11495703 | biostudies-literature