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 (<i>p</i> &lt; 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%, <i>p</i> = 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.

神经质（Neuroticism）已被证实与哮喘存在关联，但由于目前对心理因素影响哮喘风险的机制尚缺乏充分认知，二者间关联的本质仍未明确。尽管已知神经质会对多种健康结局产生影响，但其在哮喘等呼吸系统疾病中的具体作用仍未完全阐明。本研究借助全基因组关联研究（genome-wide association studies, GWAS）开展孟德尔随机化（Mendelian randomization, MR）分析，以探究12项神经质相关特质与哮喘之间的因果关联。研究采用了包括MR-PRESSO在内的多种MR分析方法，并通过独立GWAS数据集与FinnGen数据集进行验证。MR-PRESSO分析显示，情绪波动与哮喘之间存在显著的因果关联（比值比OR: 1.927，95%置信区间CI: 1.641–2.263），该结果超过了邦费罗尼校正后的显著性阈值（p值＜4.167×10⁻³）。情绪波动是唯一与哮喘显著相关的特质，反向孟德尔随机化分析未发现其余特质与哮喘存在因果关联。后续二次分析验证了上述结论。多变量分析表明，情绪波动可独立于吸烟、体重指数（Body Mass Index, BMI）与空气污染水平，增加哮喘发病风险。中介分析显示，BMI在情绪波动与哮喘的关联中发挥部分中介作用，可解释9.87%的效应（95% CI: 4.54%–15.2%，p值=2.850×10⁻⁴）。综上，情绪波动可升高哮喘发病风险，且BMI对该关联存在部分中介作用，这一发现揭示了心理特质影响哮喘发病的潜在重要通路。