Novel Digital Markers of Sleep Dynamics: A Causal Inference Approach Revealing Age and Gender Phenotypes in Obstructive Sleep Apnea

Abstract

Most individuals with sleep-disorders remain undiagnosed due to unawareness of symptoms or the high cost of polysomnographic (PSG) studies, impacting quality of life. Despite evidence that sleep-disorders alter sleep-stage-dynamics, clinical practice resists including these parameters in PSG-reports. We introduce a novel digital sleep-fingerprint, leveraging the matrix of sleep-stage-transition-proportions, enabling the derivation of several novel digital-markers and investigation of dynamics mechanisms. Using causal inference we address confounding in an observational clinical database and estimate personalized markers across ages, genders, and Obstructive-Sleep-Apnea (OSA) severities. Notably, our approach adjusts for five categories of sleep-wake-related-comorbidities, an aspect ignored in existing research, impacting 48.6% of OSA-subjects in our data. Key markers proposed, including NREM-REM-oscillations and sleep-stage-specific-fragmentations, were significantly increased across all OSA-severities and demographics. We also identified several OSA-gender-phenotypes, suggesting higher vulnerability of females to awakening and REM-sleep disruptions. Considering advances in automated-sleep-scoring and wearables, our approach can enable novel, low-cost screening tools.

Competing Interest Statement

The authors have declared no competing interest.

Funding Statement

This study did not receive any funding

Author Declarations

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

Kantonale Ethikkommission Bern (Ethical committee of the Canton Bern) gave ethical approval for this work (KEK-Nr. 2022-00415)

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Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

Yes

I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

Yes

Data Availability

All data produced in the present study are available upon reasonable request to the authors

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