Investigating the causal effects of insomnia on lung function: a two-sample Mendelian randomisation study

<bold>Background:</bold> Insomnia is associated with high morbidity, mortality, and societal costs. Few studies have suggested the link of insomnia with reduced lung function; however, it is unclear whether this is due to residual confounding or causal mechanisms. <bold>Objective:</bold> To investigate the causal effect of insomnia on lung function. <bold>Method:</bold> In this two-sample Mendelian randomization (MR) analysis, we used inverse variance weighted (IVW) method to estimate the causal effect of insomnia on lung function. We used European ancestry summary statistics from genome-wide association study (GWAS) of insomnia (Watanabe et. al. 2022, ncase=593,724, ncontrol=1,771,286, 16% were from UK Biobank) and lung function (Shrine et. al. 2023) including forced expiratory volume (FEV1, n=475,645), forced vital capacity (FVC, n=475,645), FEV1/FVC ratio (n=475,645), and peak expiratory flow (PEV, n=393,161). 326 independent single nucleotide polymorphisms (SNPs) (R2<0.001, P<5×10−8) were used as instrumental variable of insomnia. Sensitivity analyses including MR-Egger, weighted median, weighted mode, and MR-PRESSO were used to address bias due to pleiotropy. Sample overlap bias was addressed by analysing lung function summary statistics excluding UK Biobank. <bold>Result:</bold> We observed that genetic liability to insomnia is associated with reduced FEV1 (IVW beta=-0.088, 95% CI=-0.158 to -0.018) and FVC (IVW beta=-0.097, 95% CI=-0.172 to -0.022). We observed no causal association of genetic liability to insomnia with FEV1/FVC ratio (IVW beta=0.020, 95% CI=-0.045 to 0.086) and PEV (IVW beta=0.004, 95% CI=-0.058 to 0.065). <bold>Conclusions:</bold> Our findings suggest that the insomnia has a negative effect on lung functions.