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

INTRODUCTION: Numerous studies have suggested a connection between circadian rhythm and neurological disorders with cognitive and consciousness impairments in humans, yet little evidence stands for a causal relationship between circadian rhythm and the brain cortex. METHODS: The top 10,000 morningness-related single-nucleotide polymorphisms of the Genome-wide association study (GWAS) summary statistics were used to filter the instrumental variables. GWAS summary statistics from the ENIGMA Consortium were used to assess the causal relationship between morningness and variates like cortical thickness (TH) or surficial area (SA) on the brain cortex. The inverse-variance weighted (IVW) and weighted median (WM) were used as the major estimates whereas MR-Egger, MR Pleiotropy RESidual Sum and Outlier, leave-one-out analysis, and funnel-plot were used for heterogeneity and pleiotropy detecting. RESULTS: Regionally, morningness decreased SA of the rostral middle frontal gyrus with genomic control (IVW: β = −24.916 mm, 95% CI: −47.342 mm to −2.490 mm, p = 0.029. WM: β = −33.208 mm, 95% CI: −61.933 mm to −4.483 mm, p = 0.023. MR Egger: β < 0) and without genomic control (IVW: β = −24.581 mm, 95% CI: −47.552 mm to −1.609 mm, p = 0.036. WM: β = −32.310 mm, 95% CI: −60.717 mm to −3.902 mm, p = 0.026. MR Egger: β < 0) on a nominal significance, with no heterogeneity or no outliers. CONCLUSIONS AND IMPLICATIONS: Circadian rhythm causally affects the rostral middle frontal gyrus; this sheds new light on the potential use of MRI in disease diagnosis, revealing the significance of circadian rhythm on the progression of disease, and might also suggest a fresh therapeutic approach for disorders related to the rostral middle frontal gyrus-related.