Exploring the causal relationship between chronic stress and sleep apnea in human populations using Mendelian randomisation
Notice bibliographique
Résumé
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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Comment cette classification a été obtenuedéplier
Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule tête enseignante, pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».