The causal effects between selenium levels and the brain cortical structure: A two‐sample Mendelian randomization study

• Published in: Brain and behavior Vol. 13; no. 12; pp. e3296 - n/a
• Main Authors: Zhang, Xiaowei, Zhong, Yuqing, He, Kejun
• Format: Journal Article
• Language: English
• Published: United States John Wiley & Sons, Inc 01-12-2023; John Wiley and Sons Inc; Wiley
• Subjects: Alzheimer's disease; Confounding (Statistics); Cortical structure; Disease; Estimates; Genomes; Magnetic resonance imaging; Mendelian randomization analysis; Original; Oxidative stress; Selenium; Mendelian randomization analysis; Cortical structure; Selenium
• ISSN: 2162-3279; 2162-3279
• DOI: 10.1002/brb3.3296

Extensive research has demonstrated the critical role of selenium (Se) and selenoproteins in brain function and cognition. However, the impact of Se on brain cortical structure remains enigmatic. Therefore, this study used Mendelian randomization (MR) analysis to investigate the causal effect between Se levels and brain cortical structure.
Methods
This study utilizes 11 genetic variants associated with Se level variations, extracted from a large‐scale genome‐wide association study (GWAS) encompassed circulating Se levels (n = 5477) and toenail Se levels (n = 4162) in the European population. Outcome data were sourced from the summary statistics of the ENIGMA Consortium, comprising GWAS data from 51,666 individuals. The variables include cortical surface area (SA), thickness (TH) at the global level, and 34 functional cortical regions evaluated by magnetic resonance imaging. The inverse‐variance‐weighted method was used as the primary estimate. Additionally, sensitivity analyses were conducted to detect potential violations of assumptions underlying MR.
Results
At the global level, Se levels were not correlated with SA but showed a significant negative correlation with TH (β = −0.00485 mm, SE = 0.00192, p = .0115). Heterogeneity was observed across different brain regions, with positive correlations found between Se levels and the TH of the parahippocampal gyrus, superior frontal gyrus, and frontal pole, whereas negative correlations were found with the TH of the inferior parietal lobe and middle temporal lobe. Regarding SA, Se levels exhibit positive correlations with the pars triangularis, caudal anterior cingulate, inferior parietal lobe, and banks of the superior temporal sulcus. Conversely, negative correlations were observed with the medial orbitofrontal cortex, posterior cingulate gyrus, insula, and the middle, superior, and transverse gyrus of the temporal lobe. No pleiotropy was detected.
Results
This MR study indicated that Se levels causally influence the brain cortical structure.
Using Mendelian randomization analysis and data from large‐scale genome‐wide association studies and the ENIGMA consortium, this study examined the causal relationship between selenium levels and brain cortical structure. The results revealed a correlation between selenium levels and cortical thickness, with variations observed across different brain regions. These findings provide evidence for a causal effect of selenium on brain cortical structure.