The relationship between obstructive sleep apnea and osteoarthritis: evidence from an observational and Mendelian randomization study
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ABSTRACT:
SUBMITTER: Yang Z
PROVIDER: S-EPMC11239388 | biostudies-literature | 2024 Jan
REPOSITORIES: biostudies-literature
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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:BackgroundSeveral observational studies have investigated the association between myeloperoxidase (MPO) and obstructive sleep apnea (OSA). However, the nature of this relationship remains uncertain due to potential selection and confounding biases. To resolve this, we conducted a bidirectional two-sample Mendelian randomization (MR) study to scrutinize the causal relationship between MPO and OSA.MethodsInstrumental variables (IVs) for OSA were sourced from the publicly available FinnGen dataset, encompassing 38,998 OSA cases and 336,659 controls. Data on MPO were sourced from a study of 21,758 individuals conducted by the European Bioinformatics Institute (EBI). The primary MR analysis utilized the inverse-variance weighted (IVW) method, with MR-Egger intercept and leave-one-out methods assessing pleiotropy and Cochran's Q test determining heterogeneity.ResultsThe IVW analysis indicated a causal relationship between heightened MPO levels and an increased incidence of OSA. Individuals with elevated MPO levels manifested a higher propensity to develop OSA, exhibiting an odds ratio (OR) of 1.075 and a 95% confidence interval (CI) of 1.011-1.143 (p = 0.021). Conversely, the reciprocal analysis unveiled no significant association between OSA and heightened MPO levels (p = 0.643). No directional pleiotropy was identified through the MR-Egger intercept test (p > 0.05).ConclusionOur study provides evidence of an association between elevated MPO levels and an increased incidence of OSA. However, OSA does not necessarily lead to elevated MPO levels. When patients present with high MPO levels, screening for OSA may be advisable, considering their clinical characteristics.
| S-EPMC10753018 | biostudies-literature
Project description:BackgroundPrevious studies of obstructive sleep apnea (OSA) in relation to stroke have been noted. However, the exact causality remains to be clearly defined. We aimed to adopt a two-sample Mendelian randomization study to investigate the causal effects of OSA on stroke and its subtypes.MethodsA two-sample Mendelian randomization (MR) analysis was conducted to evaluate the causal effect of OSA on stroke and its subtypes, including, based on publicly genome-wide association studies (GWAS) databases. The inverse variance weighted (IVW) method was used as the main analysis. MR-Egger regression, weighted mode, weighted median, and MR pleiotropy residual sum and outlier (MR-PRESSO) were performed methods and were adopted as supplementary analysis to ensure the robustness of the results.ResultsGenetically predicted OSA was not related to the risk of stroke (odds ratio (OR), 0.99, 95% CI, 0.81-1.21, p = 0.909), and its subtypes, ischemic stroke (IS) (OR, 1.01, 95% CI, 0.82-1.23, p = 0.927), large vessel stroke (LVS) (OR, 1.05, 95% CI, 0.73-1.51, p = 0.795), cardioembolic stroke (CES) (OR, 1.03, 95% CI, 0.74-1.43, p = 0.855), small vessel stroke (SVS) (OR, 1.13, 95% CI, 0.88-1.46, p = 0.329), lacunar stroke (LS) (OR, 1.07, 95% CI, 0.74-1.56, p = 0.721) as well as intracerebral hemorrhage (ICH) (OR, 0.37, 95% CI = 0.09, 1.48, p = 0.160) (Wald ratio method). Other supplementary MR methods also confirmed similar results.ConclusionThere may be no direct causal relationship between OSA and stroke or its subtypes.
| S-EPMC10122861 | biostudies-literature
Project description:Although observational studies have reported a positive association between obstructive sleep apnea syndrome (OSAS) and breast cancer (BC) risk, causality remains inconclusive. We aim to explore whether OSAS is associated with etiology of BC by conducting a two-sample Mendelian randomization (MR) study in a Chinese population and Asian population from the Breast Cancer Association Consortium (BCAC). We found a detrimental causal effect of OSAS on BC risk in the primary analysis of our samples (IVW OR, 2.47 for BC risk per log-odds increment in OSAS risk, 95% CI = 1.86-3.27; P = 3.6×10-10). This was very similar to results of the direct observational case-control study between OSAS and BC risk (OR = 2.80; 95% CI = 2.24-3.50; P =1.4×10-19). Replication in the Asian population of the BCAC study also supported our results (IVW OR, 1.33 for BC risk per log-odds increment in OSAS risk, 95% CI = 1.13-1.56; P = 0.0006). Sensitivity analyses confirmed the robustness of our findings. We provide novel evidence that genetically determined higher risk of OSAS has a causal effect on higher risk of BC. Further studies focused on the mechanisms of the relationship between OSAS and breast carcinogenesis are needed.
| S-EPMC7093176 | 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:BackgroundPrevious studies have identified a clinical association between gut microbiota and Obstructive sleep apnea (OSA), but the potential causal relationship between the two has not been determined. Therefore, we aim to utilize Mendelian randomization (MR) to investigate the potential causal effects of gut microbiota on OSA and the impact of OSA on altering the composition of gut microbiota.MethodsBi-directional MR and replicated validation were utilized. Summary-level genetic data of gut microbiota were derived from the MiBioGen consortium and the Dutch Microbiome Project (DMP). Summary statistics of OSA were drawn from FinnGen Consortium and Million Veteran Program (MVP). Inverse-variance-weighted (IVW), weighted median, MR-Egger, Simple Mode, and Weighted Mode methods were used to evaluate the potential causal link between gut microbiota and OSA.ResultsWe identified potential causal associations between 23 gut microbiota and OSA. Among them, genus Eubacterium xylanophilum group (OR = 0.86; p = 0.00013), Bifidobacterium longum (OR = 0.90; p = 0.0090), Parabacteroides merdae (OR = 0.85; p = 0.00016) retained a strong negative association with OSA after the Bonferroni correction. Reverse MR analyses indicated that OSA was associated with 20 gut microbiota, among them, a strong inverse association between OSA and genus Anaerostipes (beta = -0.35; p = 0.00032) was identified after Bonferroni correction.ConclusionOur study implicates the potential bi-directional causal effects of the gut microbiota on OSA, potentially providing new insights into the prevention and treatment of OSA through specific gut microbiota.
| S-EPMC11414551 | biostudies-literature
Project description:BackgroundEvidence for a causal relationship between sarcopenia and obstructive sleep apnea (OSA) is scarce. This study aimed to investigate the causal association between sarcopenia-related traits and OSA utilizing Mendelian randomization (MR) analyses.MethodsMR analyses were conducted using genetic instruments for sarcopenia-related traits, including hand grip strength, muscle mass, fat mass, water mass, and physical performance. Data from large-scale genome-wide association studies (GWAS) were utilized to identify genetic variants associated with these traits. Causal associations with OSA were assessed using various MR methods, including the inverse variance-weighted (IVW) method, MR-Egger, and weighted median approaches. Pleiotropy and heterogeneity were evaluated through MR-PRESSO and other sensitivity analyses.ResultsLow hand grip strength in individuals aged 60 years and older exhibited a positive correlation with the risk of OSA (IVW, OR = 1.190, 95% CI = 1.003-1.413, p = 0.047), while no significant causal effects were observed for grip strength in the left and right hands. Muscle mass, fat mass, and water mass were significantly associated with OSA, even after adjusting for multiple testing. Notably, higher levels of body fat percentage, trunk fat percentage, and limb fat percentage were strongly correlated with increased risk of OSA. Physical performance indicators such as walking pace demonstrated an inverse association with OSA, while a higher risk of OSA was observed with increased log odds of falling risk and greater frequency of falls in the last year. Additionally, a causal effect was found between long-standing illness, disability, or infirmity and OSA.ConclusionsThis comprehensive MR analysis provides evidence of a significant causal relationship between characteristics associated with sarcopenia, including low hand grip strength, muscle mass, fat mass, and physical performance, and the risk of OSA. These findings underscore the importance of addressing sarcopenia-related factors in the management and prevention of OSA.
| S-EPMC11889072 | biostudies-literature
Project description:Observational studies indicate that the risk of prostatitis in sleep apnea patients is higher than those without sleep apnea. However, the causal relationships remain to be determined. This study aims to investigate the causal relationships of sleep apnea on prostatitis using Mendelian randomization (MR). Summary-level data for sleep apnea (16,761 cases and 201,194 controls) and prostatitis (1859 cases and 72,799 controls) were available from the GWAS summary data. Two-sample MR analyses were performed to investigate the causal relationship between sleep apnea and prostatitis. The inverse variance weighted (IVW) analysis was employed as the primary statistical method. In 2-sample MR analyses, we found that IVW estimates revealed that sleep apnea inferred an effect on risk of prostatitis at statistical significance (odds ratio [OR] = 1.370, 95% confidence interval [CI] = 0.094-0.535, P = .005). This MR study strengthens the evidence of a causal relationship between sleep apnea and prostatitis in Europeans.
| S-EPMC11651455 | biostudies-literature
Project description:Background25-hydroxyvitamin D [25(OH)D] deficiency in patients with Obstructive Sleep Apnea (OSA) has long been noted, but identifying the exact causal relationship remains hard. Investigation of the causality between 25(OH)D deficiency and OSA would help facilitate disease prevention.MethodsWe conducted a two-sample bi-directional Mendelian randomization (MR) study. For forward analysis, 237 newly identified genetic variants are used as proxies for 25(OH)D to estimate the unconfounded effect on OSA among 16,761 OSA cases and 201,194 controls of European ancestry. Reverse analysis was performed to detect the causal impact of OSA on 25(OH)D levels. The inverse variance weighted (IVW) method was used as the primary analysis. Sensitivity analysis was performed to evaluate the robustness of our results. Multivariate MR analysis was conducted to evaluate the direct link between 25(OH)D and OSA after accounting for body mass index (BMI).ResultsIVW indicated that OSA causally associated with a lower level of 25(OH)D ((β = -0.03, 95% CI = -0.06 ~ -0.007, P = 0.01). No evidence of the causal link from 25(OH)D to OSA was detected (OR = 0.99, 95% CI = 0.88 ~ 1.12, P = 0.85). Sensitivity analysis suggested the MR estimates were not biased. Multivariate MR analysis indicated the effect of OSA on 25(OH)D vanished upon accounting for BMI (β = -0.011, 95% CI = -0.028 ~ 0.007, P = 0.23).ConclusionThis MR study provided evidence that OSA was causally associated with a lower level of 25(OH)D, which might be driven by BMI. Obesity management should be enhanced in patients with OSA to prevent 25(OH)D deficiency.
| S-EPMC9569054 | 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