Neuroticism and Asthma: Mendelian Randomization Analysis Reveals Causal Link with Mood Swings and BMI Mediation

Neuroticism has been associated with asthma, but the nature of this relationship remains unclear due to limited understanding of the impact of psychological factors on asthma risk. While Neuroticism is known to affect various health outcomes, its specific role in respiratory conditions like asthma is not fully understood. We conducted Mendelian randomization (MR) analyses using genome-wide association studies (GWAS) to explore the causal link between 12 Neuroticism traits and asthma. Various MR approaches, including MR-PRESSO, were employed, with validation through independent GWAS and the FinnGen dataset. MR-PRESSO revealed a significant causal relationship between mood swings and asthma (OR: 1.927, 95% CI: 1.641–2.263), surpassing the Bonferroni-corrected threshold (p < 4.167 × 10^-³). Mood swings emerged as the only significant trait associated with asthma, with reverse MR analyses showing no causal links for other traits. Secondary analyses supported these findings. Multivariate analysis showed mood swings increased asthma risk, independent of smoking, BMI, and air pollution. Mediation analysis indicated that BMI partially mediates the mood swing-asthma relationship, accounting for 9.87% of the effect (95% CI: 4.54%–15.2%, p = 2.850 × 10⁻⁴). Mood swings elevate asthma risk, with BMI partially mediating this effect, highlighting a potentially significant pathway through which psychological traits influence asthma.