Deciphering casual association between brain structure and liver cirrhosis: Insights from Mendelian randomization

Liver cirrhosis exerts a significant influence on both the burden of family healthcare and public health expenditure. The causal relationship between brain imaging-derived phenotypes (BIDPs) and liver cirrhosis remains uncertain. This is a 2-sample Mendelian randomization (MR) study. Based on the genome-wide association study summary statistics of 1325 BIDPs and 2 cohort of liver cirrhosis traits. The main analyses were conducted using the inverse-variance weighted method. Moreover, weighted median, MR-Egger regression, weighted mode, simple mode method were also performed as sensitivity analyses. 41 BIDPs showed significant MR effects on liver cirrhosis in discovery cohort, 25 BIDPs showed significant MR effects in replication cohort. 20 BIDPs showed significant MR effects in both discovery cohort and replication cohort, with particular emphasis on the potential effects of 5 brain regions, the caudal anterior cingulate, rostral middle frontal, caudal middle frontal, isthmus cingulate, and superior frontal regions. There is a significant correlation between the structural characteristics of brain regions and the occurrence of liver cirrhosis, with close associations identified between the caudal anterior cingulate, rostral middle frontal, caudal middle frontal, isthmus cingulate, and superior frontal regions and liver cirrhosis. This study provides new insights into the brain-liver axis, suggesting that liver cirrhosis may be a disease regulated by the central nervous system.