Alcohol use habits and brain macrostructure have been linked in previous research. Due to the limits of observational research, it was challenging to pinpoint directional connections between these traits. For a study, researchers sought to determine the direction of relationships between brain shape and alcohol use using mendelian randomization (MR) and to clarify the cellular and transcriptome bases of such relationships.

Summary statistics from population-based and case-control genome-wide association studies (GWAS) of neuroimaging, behavioral, and clinical traits (N = 763,874) served as the primary source of data for the study. Bidirectional and multivariable MR was used to analyze the correlations between brain macrostructure and alcohol usage using these data. The biology behind the detected connections was further examined using downstream transcriptome-wide association studies (TWAS) and cell-type enrichment analysis. No, a priori hypotheses were tested due to the study’s data-driven methodology. Data from August 2021 to May 2022 were evaluated. Global cortical thickness [GCT] and global cortical surface area [GCSA] in 33,709 individuals and left-right subcortical volumes in 19,629 individuals were measured, as were alcohol use behaviors [alcoholic drinks per week [DPW] in 537,349 individuals, binge drinking frequency [143,685 individuals], and alcohol use disorder [8,845 individuals] compared to 20 657 control individuals [total of 29,502]].

The major bidirectional MR studies were carried out on samples totaling 763,874 people, of which more than 94% were of European ancestry, 52% to 54% were female, and the mean cohort ages were 40 to 63 years. At a false discovery rate (FDR) of 0.05, negative relationships were found between genetically predicted GCT and binge drinking (β, -2.52; 95% CI, -4.13 to -0.91) and DPW (β, -0.88; 95% CI, -1.37 to -0.40). The relationships were still significant in multivariable MR models that took into consideration neuropsychiatric traits, drug abuse, trauma, and have neurodegeneration. About 5 genes at the 17q21.31 region were shown to be oppositely linked with GCT and binge drinking or DPW (FDR = 0.05) by TWAS of alcohol use behaviors and GCT. Alcohol consumption habits were linked to glutamatergic cortical neurons by cell-type enrichment analysis.

The study’s results suggested that there may be a genetic component to the relationship between GCT and alcohol use and a potential function for glutamatergic cortical neurons and the 17q21.31 gene.