Multi-omics analysis of the causal relationship and mediation mechanisms between obstructive sleep apnea and atrial fibrillation

doi:10.11958/20250987

Abstract

Abstract:

Objective To analyse the causal relationship between obstructive sleep apnea (OSA) and atrial fibrillation (AF) by Mendelian randomization (MR) method, and to explore the role of inflammatory factors, immune cells, blood metabolites and circulating proteins in it. Methods In this study, MR analysis was used to investigate the causal link between OSA and AF. Inverse variance weighting (IVW), MR-Egger and other methods were used for sensitivity analysis. Additionally, the study also explored the effects of 91 inflammatory factors, 731 immune cells, 1 400 blood metabolites and 4 907 circulating proteins on AF. Results MR analysis revealed a significant causal relationship between OSA and AF (OR = 1.078, P<0.05). Conversely, reverse MR analysis did not find causal relationship between AF and OSA (P>0.05). Further analysis revealed that 5 inflammatory factors, 19 immune cells, 15 blood metabolites and 67 circulating proteins were risk factors for AF. Among them, OSA was the risk factor for one inflammatory factor, one blood metabolite and 12 circulating proteins. There was no significant causal association between OSA and 19 immune cells. Conclusion This study demonstrates that OSA increases the risk of AF. Meanwhile, it is found that inflammatory factors, immune cells, blood metabolites and circulating proteins have potential impacts on the pathogenesis of AF.

Key words: sleep apnea, obstructive, atrial fibrillation, Mendelian randomization analysis, inflammatory factors, immune cells, metabolites, plasma proteins

CLC Number:

R563.9

Figures/Tables 8

References 29

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暴露因素	结局	方法	SNPs/个	P	OR（95%CI）
OSA	AF	MR-Egger	41	0.479	1.091（0.859~1.387）
OSA	AF	加权中位数法	41	0.016	1.120（1.022~1.228）
OSA	AF	IVW	41	0.027	1.078（1.009~1.152）
OSA	AF	简单模式法	41	0.129	1.202（0.953~1.516）
OSA	AF	加权法	41	0.011	1.246（1.061~1.464）

暴露因素	结局	方法	SNPs/个	P	OR（95%CI）
OSA	AF	MR-Egger	41	0.479	1.091（0.859~1.387）
OSA	AF	加权中位数法	41	0.016	1.120（1.022~1.228）
OSA	AF	IVW	41	0.027	1.078（1.009~1.152）
OSA	AF	简单模式法	41	0.129	1.202（0.953~1.516）
OSA	AF	加权法	41	0.011	1.246（1.061~1.464）

暴露因素	结局	方法	SNPs/个	P	OR（95%CI）
AF	OSA	MR-Egger	87	0.343	1.037（0.962~1.118）
AF	OSA	加权中位数法	87	0.034	1.045（1.004~1.089）
AF	OSA	IVW	87	0.093	1.027（0.996~1.058）
AF	OSA	简单模式法	87	0.723	0.983（0.896~1.079）
AF	OSA	加权法	87	0.261	1.033（0.976~1.093）

暴露因素	结局	方法	SNPs/个	P	OR（95%CI）
AF	OSA	MR-Egger	87	0.343	1.037（0.962~1.118）
AF	OSA	加权中位数法	87	0.034	1.045（1.004~1.089）
AF	OSA	IVW	87	0.093	1.027（0.996~1.058）
AF	OSA	简单模式法	87	0.723	0.983（0.896~1.079）
AF	OSA	加权法	87	0.261	1.033（0.976~1.093）

暴露因素	结局	方法	SNPs/ 个	P	OR（95%CI）
成纤维细胞生长因子5	AF	IVW	28	<0.001	1.050（1.021~1.081）
白细胞介素（IL）-18 受体1	AF	IVW	33	0.006	1.048（1.013~1.083）
IL-33	AF	IVW	15	0.019	1.097（1.016~1.185）
神经营养因子3	AF	IVW	23	0.033	1.065（1.005~1.129）
血管内皮生长因子A	AF	IVW	25	0.012	1.062（1.013~1.113）