Dataset Information

Assessing the causal relationship between psychiatric disorders and obstructive sleep apnea: a bidirectional Mendelian randomization.

ABSTRACT:

Background

Extensive 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.

Methods

Mendelian 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.

Results

MR 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.

Conclusion

This 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.

SUBMITTER: Mi C

PROVIDER: S-EPMC10903261 | biostudies-literature | 2024

REPOSITORIES: biostudies-literature

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Publications

Assessing the causal relationship between psychiatric disorders and obstructive sleep apnea: a bidirectional Mendelian randomization.

Mi Chuanhao C Hou Ajiao A Liu Yinqin Y Qi Xianghua X Teng Jing J

Frontiers in psychiatry 20240214

<h4>Background</h4>Extensive 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.<h4>Methods</h4>Mendelian 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, an ...[more]

PMID: 38426001

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Project description:BackgroundObservational studies have suggested an association between obstructive sleep apnea (OSA), chronic kidney disease (CKD), and renal function, and vice versa. However, the results from these studies are inconsistent. It remains unclear whether there are causal relationships and in which direction they might exist.MethodsWe used a two-sample Mendelian randomization (MR) method to investigate the bidirectional causal relation between OSA and 7 renal function phenotypes [creatinine-based estimated glomerular filtration rate (eGFRcrea), cystatin C-based estimated glomerular filtration rate (eGFRcys), blood urea nitrogen (BUN), rapid progress to CKD, rapid decline of eGFR, urinary albumin to creatinine ratio (UACR) and CKD]. The genome-wide association study (GWAS) summary statistics of OSA were retrieved from FinnGen Consortium. The CKDGen consortium and UK Biobank provided GWAS summary data for renal function phenotypes. Participants in the GWAS were predominantly of European ancestry. Five MR methods, including inverse variance weighted (IVW), MR-Egger, simple mode, weighted median, and weighted mode were used to investigate the causal relationship. The IVW result was considered the primary outcome. Then, Cochran's Q test and MR-Egger were used to detect heterogeneity and pleiotropy. The leave-one-out analysis was used for testing the stability of MR results. RadialMR was used to identify outliers. Bonferroni correction was applied to test the strength of the causal relationships (p < 3.571 × 10-3).ResultsWe failed to find any significant causal effect of OSA on renal function phenotypes. Conversely, when we examined the effects of renal function phenotypes on OSA, after removing outliers, we found a significant association between BUN and OSA using IVW method (OR: 2.079, 95% CI: 1.516-2.853; p = 5.72 × 10-6).ConclusionThis MR study found no causal effect of OSA on renal function in Europeans. However, genetically predicted increased BUN is associated with OSA development. These findings indicate that the relationship between OSA and renal function remains elusive and requires further investigation.

Project description:BackgroundThe interactions and associations between obstructive sleep apnea (OSA), sleep-related phenotypes (SRPs), and gastroesophageal reflux disease (GERD) are complex, thus it is hard to explore the effect and direction of causalities.Study objectivesA bidirectional Mendelian randomization (MR) study was performed to explore causal associations of GERD with OSA and SRPs (including insomnia, morningness, sleep duration, ease of getting up, daytime napping, daytime dozing, and snoring).MethodsFirst, we gathered summary statistics from publicly available databases. Subsequently, we identified single-nucleotide polymorphisms without strong linkage (r2 ≤ 0.001) by referencing relevant genome-wide association studies that met genome-wide significance criteria. Our primary analysis relied on inverse variance weighted to estimate the causal relationship. To ensure the validity of our findings, we also conducted several sensitivity analyses. These included MR Pleiotropy RESidual Sum and Outlier to detect and correct for potential pleiotropic effects, MR-Egger to assess directional pleiotropy, and weighted median analysis to further evaluate heterogeneity and pleiotropy. For the initial MR analysis, when causality was indicated by the results, instrumental variables that were significantly linked to the aforementioned confounding factors were removed. We will re-analyze the data after excluding outcome-related single nucleotide polymorphisms to confirm that the results are still consistent with the previous results.ResultsGERD was found to increase the risk of OSA (OR = 1.53, 95% CI = 1.37-1.70, p = 5.3 × 10-15), insomnia (OR = 1.14, 95% CI = 1.10-1.19, p = 1.3 × 10-10), snoring (OR = 1.09, 95% CI = 1.04-1.13, p = 6.3 × 10-5) and less sleep duration (OR = 0.94, 95% CI = 0.91-0.97, p = 3.7 × 10-4). According to the reverse-direction analysis, there is an elevated risk of GERD associated with OSA (OR = 1.07, 95% CI = 1.02-1.12, p = 0.005), insomnia (OR = 1.95, 95% CI = 1.60-2.37, p = 1.92 × 10-11) and snoring (OR = 1.74, 95% CI = 1.37-2.21, p = 4.4 × 10-6).ConclusionGenetic susceptibility to GERD can elevate the likelihood of experiencing insomnia, snoring, and OSA, in addition to diminishing sleep duration. Conversely, a reverse MR analysis indicates that ameliorating any one of insomnia, snoring, or OSA can mitigate the risk of developing GERD.

Dataset Information

Assessing the causal relationship between psychiatric disorders and obstructive sleep apnea: a bidirectional Mendelian randomization.

Background

Methods

Results

Conclusion

Publications

Assessing the causal relationship between psychiatric disorders and obstructive sleep apnea: a bidirectional Mendelian randomization.

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