The genetic architecture of human cerebellar morphology supports a key role for the cerebellum in recent human evolution and psychopathology

The functional domain of the human cerebellum has expanded beyond motor control to also include cognitive and affective functions. In line with this notion, cerebellar volume has increased over recent primate evolution and cerebellar alterations have been linked to heritable mental disorders. In order to map the genetic architecture of human cerebellar morphology, we studied a large imaging genetics sample from the UK Biobank (n discovery = 27,302; n replication: 11,264) with state-of-the art neuroimaging and biostatistics tools. Multivariate GWAS (MOSTest) on empirically derived regional cerebellar MRI features yielded 351 significant genetic loci (228 novel, 94% replicated) showing both shared and specific effects across regions. Gene level analyses revealed enrichment for genes associated with human-specific evolution over the last ∼6-8 million years, to a similar or higher degree than cerebral comparison phenotypes. We also observed genetic overlap between cerebellar morphology and major mental disorders, supporting cerebellar involvement in psychopathology.