The contribution of silencer variants to human diseases.

ABSTRACT:

Background

Although disease-causal genetic variants have been found within silencer sequences, we still lack a comprehensive analysis of the association of silencers with diseases. Here, we profiled GWAS variants in 2.8 million candidate silencers across 97 human samples derived from a diverse panel of tissues and developmental time points, using deep learning models.

Results

We show that candidate silencers exhibit strong enrichment in disease-associated variants, and several diseases display a much stronger association with silencer variants than enhancer variants. Close to 52% of candidate silencers cluster, forming silencer-rich loci, and, in the loci of Parkinson's-disease-hallmark genes TRIM31 and MAL, the associated SNPs densely populate clustered candidate silencers

SUBMITTER: Huang D 

PROVIDER: S-EPMC11232194 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature