Genome-wide association study of cerebellar volume provides insights into heritable mechanisms underlying brain development and mental health

Elleke Tissink, Siemon C. de Lange, Jeanne E. Savage, Douglas P. Wightman, Christiaan A. de Leeuw, Kristen M. Kelly, Mats Nagel, Martijn P. van den Heuvel, Danielle Posthuma*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


Cerebellar volume is highly heritable and associated with neurodevelopmental and neurodegenerative disorders. Understanding the genetic architecture of cerebellar volume may improve our insight into these disorders. This study aims to investigate the convergence of cerebellar volume genetic associations in close detail. A genome-wide associations study for cerebellar volume was performed in a discovery sample of 27,486 individuals from UK Biobank, resulting in 30 genome-wide significant loci and a SNP heritability of 39.82%. We pinpoint the likely causal variants and those that have effects on amino acid sequence or cerebellar gene-expression. Additionally, 85 genome-wide significant genes were detected and tested for convergence onto biological pathways, cerebellar cell types, human evolutionary genes or developmental stages. Local genetic correlations between cerebellar volume and neurodevelopmental and neurodegenerative disorders reveal shared loci with Parkinson’s disease, Alzheimer’s disease and schizophrenia. These results provide insights into the heritable mechanisms that contribute to developing a brain structure important for cognitive functioning and mental health.
Original languageEnglish
Article number710
JournalCommunications Biology
Issue number1
Publication statusPublished - 1 Dec 2022

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