Causal associations between obstructive sleep apnea and COVID-19: A bidirectional Mendelian randomization study

Gao, Xiang; Wei, Tao; Wang, Huijun; Sui, Rongcui; Liao, Jianhong; Sun, Dance; Han, Demin

doi:10.1016/j.sleep.2022.09.013

Cited by 12 publications

(4 citation statements)

References 50 publications

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“…Previous research by Chen et al suggested that individuals with OSA may have a higher susceptibility to influenza infection due to immunodeficiency resulting from chronic sleep deprivation and stress responses 51 . However, a meta-analysis conducted by MR did not provide support for a direct causal relationship between OSA and COVID-19 52 . Therefore, the connection between OSA and sepsis appears to be intricate and potentially influenced by factors like smoking and obesity.…”

Section: Discussionmentioning

confidence: 97%

“…51 However, a meta-analysis conducted by MR did not provide support for a direct causal relationship between OSA and COVID-19. 52 Therefore, the connection between OSA and sepsis appears to be intricate and potentially influenced by factors like smoking and obesity. Additional research is warranted to elucidate any discrepancies in this association.…”

Section: Discussionmentioning

confidence: 99%

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Unveiling the Causal Association Between Noninfectious Respiratory Disorders and Sepsis Through Mendelian Randomization Analysis

Liu,

He,

Zheng

2024

Shock

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Background The association between sepsis and non-infectious respiratory diseases is well-documented, yet the specific causal link between the two remains unclear. In order to explore this relationship further, we employed a Mendelian randomization (MR) analysis utilizing data from the UK Biobank and FinnGen Biobank. Methods We analyzed the summary statistics of a genome-wide association study (GWAS) summary statistics for chronic obstructive pulmonary disease (COPD), asthma, pulmonary embolism (PE), idiopathic pulmonary fibrosis (IPF), obstructive sleep apnea (OSA), lung cancer, sepsis, and sepsis-related mortality. We employed the inverse-variance weighted (IVW) method and four additional MR methods. Heterogeneity and horizontal pleiotropy were assessed using the Cochrane's Q test, MR-Egger intercept, and MR-PRESSO test. A sensitivity analysis was also performed. Results MR analysis showed associations between COPD and lung cancer with increased sepsis risk (odds ratio (OR)IVW 1.138, P = 0.006; (OR)IVW 1.123, P = 0.031; respectively) and sepsis mortality ((OR)IVW 1.350, P = 0.022; (OR)IVW 1.312, P = 0.022; respectively). Asthma exhibited a potential protective effect against sepsis mortality((OR)IVW = 0.300, P = 0.039), while PE demonstrated a risk effect ((OR)IVW = 1.148, P = 0.032). No causal association was observed between asthma, PE, and sepsis (P > 0.05). IPF and OSA were not significantly associated with sepsis or sepsis-related mortality (P > 0.05). Heterogeneity and horizontal pleiotropy were not evident for asthma or lung cancer (P > 0.05). However, horizontal pleiotropy was suggested for COPD by the MR-Egger regression (P < 0.05), but not by the MR-PRESSO test (P > 0.05). IPF and OSA were not significantly associated with sepsis or sepsis-related mortality (P > 0.05). Conclusions Our MR analysis offers new insights into potential links between noninfectious respiratory diseases and the risk of sepsis. However, additional investigation into the underlying mechanisms and clinical studies are necessary to confirm these findings.

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Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

Unveiling the Causal Association Between Noninfectious Respiratory Disorders and Sepsis Through Mendelian Randomization Analysis

Liu,

He,

Zheng

2024

Shock

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“…Because of the random allocation of alleles at conception, MR can avoid the influence of potential confounders to logically estimate the causal sequence [24,25]. Previous studies have explored the relationship of OSA with cardiovascular disease, COVID-19, Alzheimer's disease, and Parkinson's disease [26][27][28]. And the associations between structural alterations in the brains with sleep traits such as insomnia and sleep efficiency were identified.…”

Section: Introductionmentioning

confidence: 99%

Elucidating the association of obstructive sleep apnea with brain structure and cognitive performance

Bao,

Zhao,

Qin

et al. 2024

BMC Psychiatry

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Background Obstructive sleep apnea (OSA) is a pervasive, chronic sleep-related respiratory condition that causes brain structural alterations and cognitive impairments. However, the causal association of OSA with brain morphology and cognitive performance has not been determined. Methods We conducted a two-sample bidirectional Mendelian randomization (MR) analysis to investigate the causal relationship between OSA and a range of neurocognitive characteristics, including brain cortical structure, brain subcortical structure, brain structural change across the lifespan, and cognitive performance. Summary-level GWAS data for OSA from the FinnGen consortium was used to identify genetically predicted OSA. Data regarding neurocognitive characteristics were obtained from published meta-analysis studies. Linkage disequilibrium score regression analysis was employed to reveal genetic correlations between OSA and related traits. Results Our MR study provided evidence that OSA was found to significantly increase the volume of the hippocampus (IVW β (95% CI) = 158.997 (76.768 to 241.227), P = 1.51e-04), with no heterogeneity and pleiotropy detected. Nominally causal effects of OSA on brain structures, such as the thickness of the temporal pole with or without global weighted, amygdala structure change, and cerebellum white matter change covering lifespan, were observed. Bidirectional causal links were also detected between brain cortical structure, brain subcortical, cognitive performance, and OSA risk. LDSC regression analysis showed no significant correlation between OSA and hippocampus volume. Conclusions Overall, we observed a positive association between genetically predicted OSA and hippocampus volume. These findings may provide new insights into the bidirectional links between OSA and neurocognitive features, including brain morphology and cognitive performance.

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“…Proposed mechanistic pathways underlying the observed associations include the effects of OSA on the renin–angiotensin system, sympathetic activation, inflammation, and oxidative stress ( 3 , 4 ). A small genome-wide association study reported no causal association between OSA and COVID-19 hospitalization and severity of illness ( 5 ). In contrast, a recent study from Finland that included data from the Million Veteran Program ( 6 ) reported a causal association between genetic risk factors for OSA and the risk of COVID-19 hospitalization, propagated mainly through shared genetic risk loci for obesity ( 7 ).…”

mentioning

confidence: 99%

Impact of Obstructive Sleep Apnea on Health Outcomes in Veterans Hospitalized with COVID-19 Infection

Prasad,

Mechineni,

Talugula

et al. 2024

Annals ATS

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Causal associations between obstructive sleep apnea and COVID-19: A bidirectional Mendelian randomization study

Cited by 12 publications

References 50 publications

Unveiling the Causal Association Between Noninfectious Respiratory Disorders and Sepsis Through Mendelian Randomization Analysis

Unveiling the Causal Association Between Noninfectious Respiratory Disorders and Sepsis Through Mendelian Randomization Analysis

Elucidating the association of obstructive sleep apnea with brain structure and cognitive performance

Impact of Obstructive Sleep Apnea on Health Outcomes in Veterans Hospitalized with COVID-19 Infection

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