Identifying genetic variants associated with cerebellar volume in 33,265 individuals from the UK-Biobank
Chambers, T.; Escott-Price, V.; Legge, S. E.; Baker, E.; Singh, K. D.; Walters, J. T.; Caseras, X.; Anney, R. J.
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There is expanding interest in researching the cerebellum given accumulating evidence of its important contributions to cognitive and emotional functions, in addition to more established sensorimotor roles. While large genome-wide association studies (GWAS) have shed light on the common allele architecture of cortical and subcortical brain structures, the cerebellum remains under investigated. We conducted a meta-GWAS of cerebellar volume in 33,265 UK-Biobank European participants. Results show cerebellar volume to be moderately heritable (h2SNP=50.6%). We identified 33 independent genome-wide associated SNPs with total cerebellar volume, with 6 of these SNPs mapped to protein-coding genes and 5 more shown to alter cerebellar gene expression. We highlight 21 unique candidate genes for follow-up analysis. Cerebellar volume showed significant genetic correlation with brainstem, pallidum and thalamus volumes, but no significant correlations with neuropsychiatric phenotypes. Our results provide important new knowledge of the genetic architecture of cerebellar volume and its relationship with other brain phenotypes.
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