Supplementary Material for: The lung-brain axis: genetic evidence for causal effects of asthma, allergic rhinitis, and chronic rhinosinusitis on brain structure

Background: Previous studies have indicated Asthma, allergic rhinitis (AR) and chronic rhinosinusitis (CRS) may influence brain structure. However, it remains unclear whether these three airway conditions cause brain structural changes and which specific brain regions are affected.
Methods: We conducted a Mendelian randomization (MR) to explore the causal effect of AR, CRS, and asthma on brain structure. Reverse MR was conducted to investigate potential impact of changes in brain structure on AR, CRS, and asthma. Additionally, to enhance our understanding of the lung-brain axis, we examined bidirectional relationships between Alzheimer’s disease, Parkinson’s disease, insomnia, major depression, neuroticism, attention deficit hyperactivity disorder and these three respiratory disorders
Findings: The genetically predicted CRS could reduce the surface area in the banks of the superior temporal sulcus, paracentral, and superior frontal. Asthma had an association with a decrease in the surface area of the entorhinal, fusiform, and temporal pole, as well as a reduction in the volume of amygdala. Asthma could also increase the thickness of pericalcarine. Reverse MR showed that changes in the surface area of pars opercularis and thickness of entorhinal cortex had a potential effect on CRS. Besides, bidirectional MR between 3 airway disorders and 6 neuropsychiatric disorders indicated neuroticism could raised risk for asthma, and major depression could increased the risk of CRS and asthma
Conclusion: Our MR analysis revealed a potential causal relationship among CRS, asthma, and atrophy in specific functional areas of the human brain, supporting the existence of a lung-brain axis.

背景：既往研究表明，哮喘、过敏性鼻炎（AR）和慢性鼻窦炎（CRS）可能影响大脑结构。然而，这三种气道疾病是否会导致大脑结构改变，以及哪些特定脑区受到影响，目前仍不明确。
方法：我们开展了一项孟德尔随机化（Mendelian randomization, MR）研究，以探究AR、CRS和哮喘对大脑结构的因果效应。通过反向MR分析，探讨大脑结构改变对AR、CRS和哮喘的潜在影响。此外，为深化对肺脑轴的理解，我们分析了阿尔茨海默病、帕金森病、失眠、重度抑郁症、神经质、注意缺陷多动障碍与这三种呼吸系统疾病之间的双向关系。
结果：遗传预测的CRS可减少上颞沟岸、中央旁区和上额叶的表面积。哮喘与内嗅区、梭状回和颞极的表面积减少以及杏仁核体积缩小相关。哮喘还可增加距状裂周围区的厚度。反向MR分析显示，岛盖部表面积的改变和内嗅皮层厚度的变化对CRS具有潜在影响。此外，三种气道疾病与六种神经精神疾病之间的双向MR分析表明，神经质可增加哮喘风险，重度抑郁症可提高CRS和哮喘的风险。
结论：我们的MR分析揭示了CRS、哮喘与人类大脑特定功能区萎缩之间的潜在因果关系，为肺脑轴的存在提供了支持。