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Background <p>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.</p> Methods <p>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.</p> Results <p>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, <i>p</i> = 0.023). Additionally, higher genetically predicted mode of anisotropy (MO) in the left superior thalamic radiation (STR) (OR = 0.97, <i>p</i> = 0.046) and pontine crossing tract (PCT) (OR = 0.98, <i>p</i> = 0.005), as well as increased radial diffusivity in the right superior corona radiata (SCR) (OR = 0.89, <i>p</i> = 0.009), were identified as independent protective factors against insomnia. Conclusions: 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.</p>

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

  • 期刊论文

  • 发表日期：

    2025年12月23日

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  • Hanqing Gu,
  • Ying Jiang,
  • Wentong Zhang,
  • Weiwei Li,
  • Jiejin He,
  • Sheng Liu,
  • Yong Li,
  • Chuan He

摘要

Background

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.

Methods

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.

Results

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. Conclusions: 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.