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.