Casual relationship between sepsis and cortical volume :A Bidirectional Two-sample Mendelian Randomization Study

Abstract Background The correlation between sepsis and immediate or persistent brain dysfunction has gained considerable acknowledgment within the scientific realm nowadays. Yet, the precise causal impact of sepsis on cortical volume alterations remains uncertain. Methods This two-sample bidirectional Mendelian randomization (MR) study utilized sepsis summary statistics derived from the FinnGen consortium R8 release and genome-wide association study (GWAS) summary statistics for cortical volume across various areas from the UK Biobank. The investigation explored the causal interplay between sepsis and cortical volume, employing inverse variance weighting (IVW), MR-Egger regression, weighted median, weighted model, and MR-pleiotropy residual sum and outlier (MR-PRESSO) methods. Result The study uncovered significant correlations between sepsis subtypes and changes in cortical volume across distinct brain regions. Streptococcal sepsis showed negative associations with the cortical volume of the Left Precentral Gyrus (OR: 0.99, 95%CI: 0.99–0.99, P = 1.10E− 06) and Right Cingulate Gyrus (OR: 0.93, 95%CI: 0.91–0.95, P = 1.10E− 12), while a positive link emerged with the Right Supramarginal Gyrus (OR: 1.06, 95%CI: 1.05–1.08, P = 1.60E− 21). Similarly, Pneumococcal septicemia exhibited negative correlations with cortical volume in the Left Hippocampus (OR: 0.97, 95%CI: 0.96–0.98, P = 7.50E− 08) and Right Lingual Gyrus (OR: 0.98, 95%CI: 0.97–0.99, P = 3.00E− 10). Furthermore, Other sepsis risk displayed a negative association with the Left I-IV Cerebellum (OR: 0.92, 95%CI: 0.88–0.96, P = 6.00E− 05). In the reverse MR analysis, genetic predisposition towards the Right Cuneal Cortex (OR: 0.60, 95%CI: 0.46–0.79, P = 2.70E− 04) and Right Inferior Frontal Gyrus (OR: 0.61, 95%CI: 0.48–0.78, P = 9.10E− 05) correlated strongly with Streptococcal sepsis, while genetic predisposition to the Right Thalamus (OR: 0.58, 95%CI: 0.43–0.77, P = 2.60E− 04) was notably related to Pneumococcal septicemia. Conclusion This MR study successfully unveiled a causal connection between sepsis and cortical volume across distinct brain regions. To comprehensively grasp the mechanisms underlying the impact of sepsis on cortical volume, further research endeavors are warranted.