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

## TL;DR

This study identifies genetic loci linked to cerebellar structure, showing connections to human evolution and mental disorders.

## Contribution

The study provides new insights into the genetic basis of cerebellar morphology and its evolutionary and psychiatric relevance.

## Key findings

- 351 significant genetic loci were identified, with 226 being novel and 94% replicated.
- Lead SNPs were enriched for recent genetic mutations overlapping with the Upper Paleolithic era.
- Genetic overlap with major mental disorders supports cerebellar involvement in psychopathology.

## Abstract

The functional domain of the 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. To map the genetic architecture of human cerebellar morphology, we here 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 on regional cerebellar MRI features yielded 351 significant genetic loci (226 novel, 94% replicated). Lead SNPs showed positive enrichment for relatively recent genetic mutations over the last 20-40k years (i.e., overlapping the Upper Paleolithic, a period characterized by rapid cultural evolution), while gene level analyses revealed enrichment for human-specific evolution over the last ∼6-8 million years. Finally, we observed genetic overlap with major mental disorders, supporting cerebellar involvement in psychopathology.

A multi-variate GWAS of cerebellar morphology yielded 351 genetic loci (226 novel, 94% replicated). Follow-up analyses revealed links to recent human evolution and genetic overlap with major mental disorders.