A Mendelian randomization (MR) analysis found no causal association between obstructive sleep apnea (OSA) and Alzheimer disease (AD) or Parkinson disease (PD). These findings were published in the journal Sleep Medicine.
OSA leads to recurrent oxyhemoglobin desaturation and sleep fragmentation. If untreated, OSA can contribute to mild cognitive impairment, AD, and the progression of PD. This is significant, as few individuals (an estimated 2%) with OSA are diagnosed or receive treatment. OSA is also common comorbidity among patients with PD. Despite the apparent relationship between OSA and AD or PD, it remains unclear whether there is a causal link between these conditions.
In order to evaluate whether there is a causal genetic relationship between OSA and AD or PD, researchers with the First Hospital of China Medical University and the Shengjing Hospital of China Medical University performed an MR analysis. Data were sourced from the FinnGen study, Psychiatric Genomics Consortium (PGC-ALZ), Alzheimer’s Disease Sequencing Project, International Genomics of Alzheimer’s Project, UK Biobank, and International Parkinson’s Disease Genomics Consortium. The combined sample sizes were 16,761 cases and 201,194 control individuals for OSA, 71,880 cases and 383,378 control individuals for AD, and 33,774 cases and 449,056 control individuals for PD.
There was no evidence to support a relationship between AD and OSA (odds ratio [OR], 0.99; 95% CI, 0.92-1.08). No heterogeneity of effects estimates were observed between individual variants (Q, 5.062; P =.167) nor were any outliers or pleiotropic effects found (P =.26).
Similarly, PD and OSA were not related (OR, 0.82; 95% CI, 0.47-1.4) and there was no evidence to support heterogeneity or pleiotropy (P =.144).
The major limitation of this study was that the full summary genome-wide association study statistics for OSA were unavailable, making it impossible to perform a multivariable and mediation MR analysis which would have evaluated the indirect and direct causal links between OSA and AD or PD.
“The present study found no evidence for causal associations between OSA and the risk
of AD or PD in individuals of European ancestry,” the researchers stated.
They believe their findings suggest that “observed associations between OSA and AD, PD might be driven by reverse causation or potential confounders, probably due to multiple mechanisms including the deleterious effects of its vascular comorbidities, disruption of sleep, intermittent hemodynamic and hypoxia changes, and common risk factors.”
Li J, Zhao L, Ding X, Cui X, Qi L, Chen Y. Obstructive sleep apnea and the risk of Alzheimer’s disease and Parkinson disease: A Mendelian randomization study OSA, Alzheimer’s disease and Parkinson disease. Sleep Med. Published online June 9, 2022. doi:10.1016/j.sleep.2022.06.004