Shared sets of correlated polygenic risk scores and voxel-wise grey matter across multiple traits identified via bi-clustering.

Abstract

Neuropsychiatric disorders involve complex polygenic determinants as well as brain alterations. The combination of genetic inheritance and neuroimaging approaches could advance our understanding of psychiatric disorders. However, cross-disorder overlap is a current issue since psychiatric conditions share some neurogenetic correlates, symptoms, and brain effects. Exploring the impact of genetic risk on the brain across disorders could help understand commonalities across multiple psychopathologies. To do this, we first compute the linear relationship between PRS and voxel-wise grey matter volume to generate brain maps for five psychiatric and three control traits. Next, we use the biclustering approach to identify regions of the brain associated with polygenic risk scores in one or more traits. Our results demonstrate a significant overlap in brain regions connected to polygenic risk across psychiatric traits. Moreover, such brain domains are highly allied with the polygenic risk for non-psychiatric control traits. This multi-trait overlap characterizes the nonspecific relationship between neural anatomy and inherited risk factors in psychiatric conditions, and in some cases, the overlap in neural features linked to genetic risk for non-psychiatric attributes.Clinical Relevance-This study presents biclusters of multiple psychiatric and control traits. The analysis reported various brain regions, including cerebellum, cuneus, precuneus, fusiform, supplementary motor area, that show significant correlation with polygenic risk scores across diverse groups of psychiatric conditions and non-psychiatric control traits.