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Integrative functional genomics reveals transcriptional regulatory function of risk alleles for metabolic liver disease

ABSTRACT: Genome-wide association studies (GWAS) have identified nearly 100 loci associated with metabolic dysfunction-associated steatotic liver disease (MASLD), but the molecular functions of these variant alleles remain elusive, particularly when they occur in non-coding regions. Here we profiled the chromatin landscape of liver nuclei from 12 individuals with varying stages of metabolic liver disease, which provide a global regulatory program in liver. Then we used massively parallel reporter screen to identify differential activity variants (DAVs). The target genes of these DAVs were delineated by expression quantitative trait loci (eQTLs), chromatin loops and single-cell CRISPRi screening. These multimodal integration analyses provide insights into the regulatory mechanisms of MASLD progression driven by genetic risks.

ORGANISM(S): Escherichia coli Homo sapiens

PROVIDER: GSE281364 | GEO | 2026/03/16

REPOSITORIES: GEO

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