The causality between leisure sedentary behaviors, physical activity and obstructive sleep apnea: a bidirectional Mendelian randomization study
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ABSTRACT:
SUBMITTER: Tian H
PROVIDER: S-EPMC11224541 | biostudies-literature | 2024 Jan
REPOSITORIES: biostudies-literature
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Project description:Background: Multiple observational studies have discovered a substantial link between obstructive sleep apnea (OSA) and ventricular dysfunction. However, conventional observational studies are vulnerable to causal reversal and confounding, making it challenging to infer the causes of effects and their direction. Methods: With the help of a bidirectional, two-sample Mendelian randomization (MR) study, we assessed the potential causality between OSA and left and right ventricular (LV, RV) structure and function. We conducted our analysis utilizing summary data from genome-wide association studies of OSA (16,761 cases and 201,194 controls) in the FinnGen Study, as well as LV (36,041 participants) and RV (29,506 participants) in the UK Biobank cardiovascular magnetic resonance research. The inverse variance weighted (IVW) was selected as the main strategy, with the MR-Egger and weighted median methods serving as supplements. Other methods were employed as sensitivity analysis tools to look at heterogeneity and pleiotropy, including MR-Egger intercept, Cochran Q statistic, MR-PRESSO, and leave-one-out analysis. Results: In the primary IVW analysis, genetically predicted OSA was strongly causative on LV end-diastolic volume (β = 0.114, 95% CI = 0.034-0.194, p = 0.006) and LV stroke volume (β = 0.111, 95% CI = 0.031-0.191, p = 0.007), and genetically predicted LV ejection fraction was linked to an increased risk of OSA (OR = 1.161, 95% CI = 1.029-1.309, p = 0.015). However, there was no connection found between OSA and any RV parameters. Conclusion: Our genetic analysis raises a potential causative link between OSA and ventricular structure and function, which may improve the knowledge of OSA as a risk factor for cardiovascular disease by demonstrating a direct impact on cardiac structure and function.
| S-EPMC10597648 | biostudies-literature
Project description:Various studies have highlighted the important associations between obstructive sleep apnea (OSA) and gut microbiota and related metabolites. Nevertheless, the establishment of causal relationships between these associations remains to be determined. Multiple mendelian randomization (MR) analyses were performed to genetically predict the causative impact of 196 gut microbiota and 83 metabolites on OSA. Two-sample MR was used to assess the potential association, and causality was evaluated using inverse variance weighted (IVW), MR-Egger, and weighted median (WM) methods. Multivariable MR (MVMR) was employed to ascertain the causal independence between gut microbiota and the metabolites linked to OSA. Additionally, Cochran's Q test, the MR Egger intercept test and the MR Steiger test were used for the sensitivity analyses. The analysis of the 196 gut microbiota revealed that genus_Ruminococcaceae (UCG009) (PIVW = 0.010) and genus_Subdoligranulum (PIVW = 0.041) were associated with an increased risk of OSA onset. Conversely, Family_Ruminococcaceae (PIVW = 0.030), genus_Coprococcus2 (PWM = 0.025), genus_Eggerthella (PIVW = 0.011), and genus_Eubacterium (xylanophilum_group) (PIVW = 0.001) were negatively related to the risk of OSA. Among the 83 metabolites evaluated, 3-dehydrocarnitine, epiandrosterone sulfate, and leucine were determined to be potential independent risk factors associated with OSA. Moreover, the reverse MR analysis demonstrated a suggestive association between OSA exposure and six microbiota taxa. This study offers compelling evidence regarding the potential beneficial or detrimental causative impact of the gut microbiota and its associated metabolites on OSA risk, thereby providing new insights into the mechanisms of gut microbiome-mediated OSA development.
| S-EPMC10648878 | biostudies-literature
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 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:PurposeThis study aims to assess the causal relationship between Obstructive Sleep Apnea (OSA), dyslipidemia, and osteoporosis using Mendelian Randomization (MR) techniques.MethodsUtilizing a two-sample MR approach, the study examines the causal relationship between dyslipidemia and osteoporosis. Multivariable MR analyses were used to test the independence of the causal association of dyslipidemia with OSA. Single nucleotide polymorphisms (SNPs) were selected as instrumental variables based on genome-wide significance, independence, and linkage disequilibrium criteria. The data were sourced from publicly available Genome-Wide Association Studies (GWAS) of OSA (n = 375,657) from the FinnGen Consortium, the Global Lipids Genetics Consortium of dyslipidemia (n = 188,577) and the UK Biobank for osteoporosis (n = 456,348).ResultsThe MR analysis identified a significant positive association between genetically predicted OSA and triglyceride levels (OR: 1.15, 95% CI: 1.04-1.26, p = 0.006) and a negative correlation with high-density lipoprotein cholesterol (HDL-C) (OR: 0.84, 95% CI: 0.77-0.93, p = 0.0003). Conversely, no causal relationship was found between dyslipidemia (total cholesterol, triglycerides, HDL-C, and low-density lipoprotein cholesterol) and OSA or the relationship between OSA and osteoporosis.ConclusionThe study provides evidence of a causal relationship between OSA and dyslipidemia, highlighting the need for targeted prevention and management strategies for OSA to address lipid abnormalities. The absence of a causal link with osteoporosis and in the reverse direction emphasizes the need for further research in this area.
| S-EPMC11222592 | biostudies-literature
Project description:(1) Background: Increasing evidence shows that sedentary behaviors are associated with neuropsychiatric disorders (NPDs) and thus may be a modifiable factor to target for the prevention of NPDs. However, the direction and causality for the relationship remain unknown; sedentary behaviors could increase or decrease the risk of NPDs, and/or NPDs may increase or decrease engagement in sedentary behaviors. (2) Methods: This Mendelian randomization (MR) study with two samples included independent genetic variants related to sedentary behaviors (n = 408,815), Alzheimer's disease (AD; n = 63,926), schizophrenia (SCZ; n = 105,318), and major depressive disorder (MDD; n = 500,199), which were extracted from several of the largest non-overlapping genome-wide association studies (GWASs), as instrumental variables. The summarized MR effect sizes from each instrumental variable were combined in an IVW (inverse-variance-weighted) approach, with various approaches (e.g., MR-Egger, weighted median, MR-pleiotropy residual sum and outlier), and sensitivity analyses were performed to identify and remove outliers and assess the horizontal pleiotropy. (3) Results: The MR evidence and linkage disequilibrium score regression revealed a consistent directional association between television watching and MDD (odds ratio (OR), 1.13 for MDD per one standard deviation (SD) increase in mean television watching time; 95% CI, 1.06-1.20; p = 6.80 × 10-5) and a consistent relationship between computer use and a decrease in the risk of AD (OR, 0.52 for AD per one SD increase in mean computer use time; 95% CI, 0.32-0.84; p = 8.20 × 10-3). In the reverse direction, MR showed a causal association between a reduced risk of SCZ and an increase in driving time (β, -0.016; 95% CI, -0.027--0.004; p = 8.30 × 10-3). (4) Conclusions: Using genetic instrumental variables identified from large-scale GWASs, we found robust evidence for a causal relationship between long computer use time and a reduced risk of AD, and for a causal relationship between long television watching time and an increased risk of MDD. In reverse analyses, we found that SCZ was causally associated with reduced driving time. These findings fit in with our observations and prior knowledge as well as emphasizing the importance of distinguishing between different domains of sedentary behaviors in epidemiologic studies of NPDs.
| S-EPMC9223103 | 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: Not available
| S-EPMC11239387 | biostudies-literature
Project description:BackgroundObservational studies have suggested that sedentary behaviors and sleep status are associated with frailty. However, it remains unclear whether these associations are causal.MethodsUsing summary statistics from genome-wide association studies, we evaluated the causal effect of modifiable risk factors, including leisure sedentary behaviors and sleep status on the frailty index (FI) using two-sample univariable and multivariable Mendelian randomization (MR) analyses. Genetic correlations were tested between the correlated traits.ResultsWe identified potential causal associations between the time spent watching television (β = 0.26, 95% confidence interval [CI]: 0.21-0.31, P = 3.98e-25), sleep duration (β = -0.18, 95%CI: -0.26, -0.10; P = 6.04e-06), and daytime napping (β = 0.29, 95%CI: 0.18-0.41, P = 2.68e-07) and the FI based on the inverse-variance-weighted method. The estimates were consistent across robust and multivariate MR analyses. Linkage disequilibrium score regression detected a genetic correlation between the time spent watching television (Rg = 0.43, P = 6.46e-48), sleep duration (Rg = -0.20, P = 5.29e-10), and daytime napping (Rg = 0.25, P = 3.34e-21) and the FI.ConclusionsGenetic predispositions to time spent watching television and daytime napping were positively associated with the FI, while sleep duration was negatively associated with the FI. Our findings offer key insights into factors influencing biological aging and suggest areas for interventions to promote healthy aging and slow down the aging process.
| S-EPMC10874533 | 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