Causal relationships between cerebral cortical architecture and blood cancers: the disease spectrum is different because the brains look different

Abstract Purpose Little is known about how the brain regulates extracerebral tumors. There is a significant difference in the incidence of hematologic maligancies between Han Chinese and European/American populations, with the most pronounced difference being more than 8–10 fold for multiple myeloma (MM) and chronic lymphocytic leukemia (CLL). Here, we aimed to investigate the genetic predisposition specific to each hematologic malignancy and to determine whether variations in cortical architecture contribute to population-level differences in their incidence. Methods In this study, we investigated causal relationships between cortical structural characteristics and eight hematologic malignancies using Mendelian randomization analyses based on data from the ENIGMA3, CHIMGEN, and FinnGen cohorts. Results MM showed a positive association with the surface area of the pars triangularis, whereas CLL was positively associated with the cortical thickness of the rostral anterior cingulate and rostral middle frontal regions. In addition, European/American populations exhibited a larger pars triangularis surface area and greater thickness of the rostral anterior cingulate and rostral middle frontal compared with Han Chinese populations. Findings from pathway analysis and transcriptome-wide association study provided additional evidence supporting these causal associations. Conclusions This study provides the first evidence examining the impact of cortical structural features on specific extracerebral cancer types. The findings further suggest that variations in cortical architecture may contribute to ancestry-related differences in the incidence of certain hematologic malignancies.