Abstract
BACKGROUND: Alterations in the central nervous system of patients with asthma have been reported. However, the intricate relationship between asthma and cortical structure remains unclear and challenging to determine. To determine the association between asthma and changes in brain cortical structure, we conducted a two-sample Mendelian randomization study. METHODS: Genome-wide association studies summary data of asthma in 408,442 participants from the UK Biobank were used to identify genetically predicted asthma. Uncorrelated (r(2) < 0.001) single nucleotide polymorphisms (SNPs) were selected as instrumental variants. Cortical thickness and surface area were obtained from 51,665 patients from the ENIGMA Consortium as outcomes in this study. Inverse-variance weighted was employed as the primary estimate whereas MR Pleiotropy RESidual Sum and Outlier, MR-Egger, and weighted median were used to detect heterogeneity and pleiotropy. RESULTS: At the global level, no statistically significant association was observed between asthma and global surface area or cortical thickness. In region-specific analyses, nominal significant associations were identified between asthma and the surface area of the parahippocampal gyrus, both with global weighting (β = 5.07 mm², 95% CI: 0.80 to 9.33, P = 0.0198) and without global weighting (β = 5.92 mm², 95% CI: 0.77 to 11.07, P = 0.0242), as well as with the cortical thickness of the caudal anterior cingulate gyrus, both with global weighting (β = -0.01 mm, 95% CI: -0.02 to -0.001, P = 0.0243) and without global weighting (β = -0.01 mm, 95% CI: -0.02 to -0.001, P = 0.0259). However, none of these associations remained statistically significant after adjustment for multiple comparisons. CONCLUSIONS: This two-sample Mendelian randomization analysis did not identify a statistically significant association between asthma and global cortical metrics. While nominal associations were observed between asthma and changes in parahippocampal and caudal anterior cingulate, these findings did not remain significant after correction for multiple comparisons and should be interpreted as exploratory. Further research is needed to elucidate potential neuroanatomical alterations associated with asthma.