Psychiatric disorders such as schizophrenia are commonly associated with structural brain alterations affecting the cortex. Recent genetic evidence suggests circulating metabolites and other biochemical traits play a causal role in many psychiatric disorders which could be mediated by changes in the cerebral cortex. Here, we leveraged publicly available genome-wide association study data to explore shared genetic architecture and evidence for causal relationships between a panel of 50 biochemical traits and measures of cortical thickness and surface area. Linkage disequilibrium score regression identified 191 genetically correlated biochemical-cortical trait pairings, with consistent representation of blood cell counts and other biomarkers such as C-reactive protein (CRP), haemoglobin and calcium. Spatially organised patterns of genetic correlation were additionally uncovered upon clustering of region-specific correlation profiles. Interestingly, by employing latent causal variable models, we found strong evidence suggesting CRP and vitamin D exert causal effects on region-specific cortical thickness, with univariable and multivariable Mendelian randomization further supporting a negative causal relationship between serum CRP levels and thickness of the lingual region. Our findings suggest a subset of biochemical traits exhibit shared genetic architecture and potentially causal relationships with cortical structure in functionally distinct regions, which may contribute to alteration of cortical structure in psychiatric disorders.
© 2022. The Author(s).