Objective  To explore the potential bidirectional causality between atrial fibrillation (AF)/atrial flutter (AFL) and insomnia by two sample Mendelian randomization (MR).

Methods  The summary data for AF/AFL and insomnia were obtained from the genome-wide association study (GWAS) in IEU OpenGWAS project databases respectively. Significant and independent single nucleotide polymorphisms (SNPs) were extracted for MR analysis. Inverse-variance weighted (IVW), weighted median (WM), MR-Egger, simple mode and weighted mode were used to assess causality. In addition, the heterogeneity of IVW was examined by Cochran's Q test, MR-Egger test was used to detect horizontal pleiotropy, the outliers were detected by MR-PRESSO method to test gene pleiotropy and the leave-one-out sensitivity analysis was conducted to ensure result robustness.

Results  With AF/AFL as exposure and insomnia as outcome, a total of 47 SNPs were screened as instrumental variables, and IVW showed a positive causal relationship between AF/AFL and insomnia[OR=1.103, 95%CI(1.008, 1.208), P<0.05]. The β values were in the same direction of WM, MR-Egger, simple mode and weighted mode with that of IVW. Sensitivity analysis shows that there was no heterogeneity in the results of Cochran's Q test (P>0.05), and MR-Egger test (P>0.05) indicated that there was no horizontal pleiotropy. At the same time, no outlier value was detected by MR-PRESSO method, and there was no gene pleiotropy. No SNP was tested with leave-one-out method, indicating that the results were robust and unbiased. When insomnia as exposure and AF/AFL as outcome, a total of 12 SNPs were screened as instrumental variables, and IVW showed there was no causal relationship between insomnia and AF/AFL[OR=0.989, 95%CI(0.951, 1.029), P>0.05].

Conclusion  AF/AFL will increase the risk of insomnia. In the management of insomnia patients,  common arrhythmia diseases such as AF and AFL should be actively prevented and treated.

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