Gene expression profiles complement the analysis of genomic modifiers of the clinical onset of Huntington disease.

ABSTRACT: Huntington disease (HD) is a neurodegenerative disorder that is caused by a CAG repeat expansion in HTT. The length of this repeat, however, only explains a proportion of the variability in age of onset in patients. Genome-wide association studies have identified modifiers that contribute toward a proportion of the observed variance. By incorporating tissue-specific transcriptomic information with these results, additional modifiers can be identified. We performed a transcriptome-wide association study assessing heritable differences in genetically determined expression in diverse tissues, with genome-wide data from over 4000 patients. Functional validation of prioritized genes was undertaken in isogenic HD stem cells and patient brains. Enrichment analyses were performed with biologically

SUBMITTER: Wright GEB 

PROVIDER: S-EPMC7530525 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature