In a recent study published in The Lancet Regional Health, researchers conducted a Mendelian Randomization (MR) analysis to understand the causal effect of snoring on overall stroke, hemorrhagic stroke (HS), and ischemic stroke (IS) in Chinese adults, using data from the China Kadoorie Biobank (CKB).
Studie: Kausaler Zusammenhang zwischen Schnarchen und Schlaganfall: eine Mendelsche Randomisierungsstudie in einer chinesischen Bevölkerung. Bildnachweis: F01 PHOTO/Shutterstock.com
While MR studies have examined the association between snoring and stroke in the European population, data for the Asian population are scarce, partly due to the unavailability of genetic variants. Observational studies on the relationship between snoring and stroke in individuals of different descent have yielded inconclusive results.
It is important to note that snoring can trigger a stroke through multiple pathways, such as causing anoxemia, oxidative stress reactions, and endothelial disturbances leading to atherosclerosis and stroke. Additionally, snoring can transmit strong vibration to the carotid artery and trigger a cascade effect on arterial wall cells, potentially leading to a vessel rupture.
In this study, researchers constructed genetic risk scores (GRS) based on single nucleotide polymorphisms (SNPs) from the genome-wide association analysis (GWAS) of snoring in CKB and UK Biobank participants. They used these data to draw a causal inference on snoring with stroke in Chinese adults aged 30 to 79 years living in ten study areas across China.
The multivariable MR (MVMR) included additional adjustments for the GRS of body mass index (BMI) and used SNPs from CKB, UKB, and Biobank Japan. The study participants self-reported their snoring status in the baseline survey, classifying those reporting frequent or occasional snoring as snorers and others as non-snorers.
The study outcomes were stroke, HS, and IS. The researchers validated the register and insurance-based definition for stroke cases and confirmed a diagnosis confirmation rate of 91.8% by reviewing medical records.
During the statistical analysis, the team used Efron pseudo-R2 and F statistics to estimate the variance explained by GRS for snoring and employed a two-step method to determine the causal hazard ratio (HR) considering multiple factors.
Furthermore, the team used MR with the inverse variance weighting (IVW) method to investigate the causal effect of snoring on stroke using three SNPs identified as genetic instrumental variables for snoring in the CKB-GWAS. They tested pleiotropy and heterogeneity using MR-Egger regression and Cochranes Q-tests, with sensitivity analysis excluding SNPs associated with obesity.
Results and Conclusion
The present MR analysis of snoring and stroke included 82,339 independent participants of Asian descent in CKB with baseline and genotyping data. Over a mean follow-up time of 10.10 years, 19,623 strokes occurred, including 11,483 IS cases and 5710 HS cases. The MR-Egger regression test showed no horizontal pleiotropy (P > 0.05), and the Cochrane Q-test revealed no heterogeneity (P > 0.05).
The results confirmed a positive association between snoring and overall stroke, as well as HS and IS with respective HRs (95% CIs) of 1.56, 1.50, and 2.02 using the GRS of 100,626 CKB participants. Likewise, the corresponding HRs using the GRS of UKB were 1.78, 1.94, and 1.74.
Obesity, causing fat deposition near the upper airway structures or tongue, leads to snoring. Some studies have shown that oropharyngeal exercises and mandibular advancement devices can treat snoring. In this study, the researchers conducted several consecutive analyses to eliminate the distorting tendency caused by obesity, observing that these associations remained stable in the MVMR analysis, IVW method MR, and the non-obese group (BMI < 24.0 kg/m²). This suggests that BMI pleiotropy did not influence the causal effect of snoring on stroke.
As a result, the researchers concluded that snoring interventions targeting the management of physical structures may be more beneficial in stroke prevention than weight management.
Overall, this study found that snoring is a potential causal factor for increased risk of stroke and its subtypes in Chinese adults, independent of the impact of BMI, a well-established factor for strokes.