Exploring the causal relationship between chronic stress and sleep apnea in human populations using Mendelian randomisation
Bibliographic record
Abstract
Background: Sleep apnea (SA) is a major respiratory disorder affecting nearly 1 billion adults worldwide. It is characterised by frequent respiratory arrests during sleep that are associated with recurrent O 2 desaturations. Because it disrupts sleeps and causes intermittent hypoxia, SA increases the risk of numerous diseases including obesity, hypertension, depression, and cancer. Despite its clinical and economical impacts, continuous positive airway pressure device remains the main treatment option for SA. A limited understanding of the origins of the disease impedes the development of novel treatments. Stress-related mental health issues such as anxiety and post-traumatic stress disorders (PTSD) double the risk of SA. While animal studies indicate that chronic stress exposure can cause the development of SA, this concept is difficult to test in observational studies in humans owing the numerous confounding factors related to lifestyle (diet, alcohol, sedentarity). To circumvent this limitation, we used Mendelian Randomisation (MR), an approach that uses natural genetic variation in human populations to explore causal relationships between risk factors and known medical conditions. Hypothesis: Clinical conditions associated with chronic stress cause SA. Methods: The association between seven stressful / stress-related risk factors such as social isolation (SI), depression, anxiety and SA was evaluated. Independent genetic variants (single nucleotide polymorphisms) strongly associated to risk factors were obtained from 16 genome-wide association study (GWAS) summary statistics from different biobanks of European cohorts (~100 000 to 1,096,458 participants). The primary analysis chosen was the inverse-variance weighted estimator to investigate the effect of the different exposures on SA. Additional MR analyses were performed to unravel the direct causal effect of anxiety or SI independently of obesity on SA. Results: We identified significant correlations between SA and SI (Odds ratio (OR): 1.96, 95% confidence interval (CI): 1.45 – 2.64, P = 1.11x10 -05 ), anxiety (OR: 2.44, 95% CI: [1.72 – 3.47], P = 6.37 x10 -07 ). After adjusting for BMI or body fat percentage using multivariable MR analysis, the causal effect of SI on SA remained significant (respectively, OR:1.48, 95% CI: [1.08-2.03]; P=0.016, and OR:1.35, 95% CI: [1.41-2.84]; P=1.26x10 -04 ). Conclusion: Results from this MR study indicate that chronic stress, especially SI and anxiety, is causally related to SA; in some cases, it may be a modifiable risk factor. Regardless, it is a new target in the prevention and detection of SA. Addressing the underlying neuroendocrine mechanisms represents a promising avenue for the development of focused therapeutic strategies to alleviate SA. Supported by the Canadian Institutes of Health Research and the Foundation of the Québec Heart & Lung Institute This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".