Shared and unique 3D genomic features of substance use disorders across multiple cell types.

ABSTRACT: Recent genome-wide association studies (GWAS) revealed shared genetic components among substance use disorders (SUDs). However, the extent of underlying shared causal variants, effector genes, and cellular contexts, remain unclear. We integrated 3D genomic datasets (high-resolution promoter-focused Capture-C/Hi-C, ATAC-seq, RNA-seq) from 59 diverse human cell types with recent GWAS summary statistics for alcohol (AUD), tobacco (TUD), opioid (OUD), and cannabis use disorder (CanUD). Using stratified LD regression, we determined the proportion of SNP heritability attributable to features in these cell types. We observed significant enrichments (P<0.05) in 25 cell types. Heritability reached 4.2-fold enrichment for CanUD in iPSC-derived cortical neurons and 6-fold for AUD/TUD in neural

SUBMITTER: Trang KB 

PROVIDER: S-EPMC11275669 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature