Being a morning man has causal effects on the cerebral cortex: a Mendelian randomization study

Area of Science:

• Neuroscience
• Genetics
• Chronobiology

Background:

• Existing research links circadian rhythm disruptions to neurological disorders affecting cognition and consciousness.
• However, direct causal evidence connecting circadian rhythm to specific brain cortex structures remains limited.

Purpose of the Study:

• To investigate the causal relationship between morningness (a measure of circadian preference) and brain cortical surface area (SA) and thickness (TH).
• To identify specific brain regions potentially affected by circadian rhythm variations.

Main Methods:

• Utilized Genome-wide association study (GWAS) summary statistics for morningness-related single-nucleotide polymorphisms.
• Employed Mendelian randomization (MR) analysis, including inverse-variance weighted (IVW) and weighted median (WM) methods.
• Assessed heterogeneity and pleiotropy using MR-Egger, MR-PRESSO, leave-one-out analysis, and funnel plots.

Main Results:

• Morningness was causally associated with a decreased surface area (SA) in the rostral middle frontal gyrus.
• This effect was observed both with and without genomic control, with statistically significant p-values.
• No significant heterogeneity or outliers were detected, supporting the robustness of the findings.

Conclusions:

• Circadian rhythm, specifically morningness, causally impacts the rostral middle frontal gyrus's surface area.
• This establishes a direct link between circadian rhythm and brain cortex structure.
• Findings may inform MRI-based disease diagnosis, disease progression understanding, and novel therapeutic strategies for related neurological disorders.