Investigating the causal relationship between multimodal brain imaging-derived phenotypes and insomnia: A Mendelian...

Insomnia has been consistently linked to alterations in both the structural and functional characteristics of the brain, yet the precise causal mechanisms underlying these associations remain incompletely understood.

We used genome-wide association study (GWAS) summary data for 3,935 multimodal IDPs from 22,138 individuals and insomnia data from 283,595 individuals. Univariate bidirectional and multivariable Mendelian randomization (MR) analyses were performed to assess causal relationships, including independent effects.

After multiple comparison corrections, univariate variable that showed significant associations were included in the multivariable MR analysis. The results indicated that a higher genetically predicted surface area of the left supramarginal gyrus was an independent risk factor for increased insomnia prevalence (OR = 3.73, p = 0.023). Additionally, higher genetically predicted mode of anisotropy (MO) in the left superior thalamic radiation (STR) (OR = 0.97, p = 0.046) and pontine crossing tract (PCT) (OR = 0.98, p = 0.005), as well as increased radial diffusivity in the right superior corona radiata (SCR) (OR = 0.89, p = 0.009), were identified as independent protective factors against insomnia.

This study offers causal neuroimaging evidence supporting the involvement of cortical and white matter structures, including the supramarginal gyrus, STR, PCT, and SCR, in the pathogenesis of insomnia. Future research is needed to evaluate whether targeting these regions could hold therapeutic potential.