Genetic Association of Mood Swings with Lung Function and Respiratory Diseases

<b>Background:</b> Observational studies have linked psychotic disorders to impaired lung function and respiratory diseases, but the potential association between mood swings-a potential predisposing factor for psychotic disorders-and lung health remains poorly understood. <b>Methods:</b> Using summary-level data from large-scale genome-wide association studies, we investigated the shared genetic basis and putative causal links between mood swings and lung function, asthma, and chronic obstructive pulmonary disease (COPD). <b>Results:</b> Evident genetic correlations in our study were observed between mood swings and FEV1 (<i>r_g</i> = -0.09), FVC (<i>r_g</i> = -0.09), PEF (<i>r_g</i> = -0.09), asthma (<i>r_g</i> = 0.33), and COPD (<i>r_g</i> = 0.28). Local genetic correlation analysis identified 10 significant local genomic regions, including chr17p12-p11.2 and chr16q23.1. Furthermore, cross-trait meta-analysis revealed 55 SNPs shared between mood swings and lung function, 2 SNPs with asthma, and 1 SNP with COPD. A transcriptome-wide association study identified 43 shared genes that largely overlapped with those revealed in the cross-trait meta-analysis, implicating tissues in the nervous, respiratory, digestive, and cardiovascular systems. Mendelian randomization analysis provided evidence that mood swings are significantly linked to reduced FEV1 (OR = 0.85, 95% CI = 0.77-0.93), reduced FVC (OR = 0.86, 95% CI = 0.77-0.96), reduced PEF (OR = 0.82, 95% CI = 0.74-0.91), and an elevated risk of asthma (OR = 2.22, 95% CI = 1.60-3.06) and COPD (OR = 2.02, 95% CI = 1.37-2.98). <b>Conclusions:</b> This study highlights a shared genetic basis and putative causal relationship between mood swings and impaired lung function and respiratory diseases, providing genetic evidence that underscores the importance of investigating mood instability in the context of respiratory health.