ArticleSleep advances : a journal of the Sleep Research Society2026
A polygenic risk score modifies the cardiovascular risk associated with obstructive sleep apnea.
Article in Sleep advances : a journal of the Sleep Research Society, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Study Objectives: Obstructive sleep apnea (OSA) carries increased cardiovascular (CV) risk. However, this risk is not fully captured by the apnea-hypopnea index (AHI). We investigated whether a validated coronary artery disease polygenic risk score (CAD-PRS) refines CV risk assessment in OSA. Methods: We derived CAD-PRS using genome-wide genotyping data for 1379 participants of the CoLaus|HypnoLaus cohort who underwent polysomnography. Associations between OSA, CAD-PRS, clinical factors, and incident CV events were assessed using multivariable Cox proportional hazards models. Risk stratification improvement was assessed with reclassification analyses compared to clinical risk scores (SCORE2/SCORE2-OP). Results: During 7.2 years of median follow-up, 100 participants experienced CV events. A significant interaction between OSA and CAD-PRS was observed (p=.013). The effect of OSA on CV risk differed across PRS categories. In the intermediate genetic-risk group (CAD-PRS quintiles 2-4), OSA patients (AHI ≥15/h) had a markedly higher CV risk compared to non-OSA (HR[95% CI]: 2.68[1.54-4.66]), whereas OSA did not significantly increase CV risk in either the low or high PRS strata. The complete model with OSA, CAD-PRS and their interaction allowed a significant reclassification (Net Reclassification Index 0.171, p=.014) compared to SCORE2/SCORE2-OP and 52% of individuals at intermediate risk were reclassified as low or high CV risk. Conclusions: In this population-based cohort, a CAD-PRS was associated with CV risk stratification in individuals with OSA. The impact of OSA on CV risk was greatest in individuals with intermediate genetic risk. Adding CAD-PRS and OSA to SCORE2 was associated with improved model performance and reclassification, supporting more precise CV risk assessment in OSA.
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