Integrative single-cell multi-omics profiling of human pancreatic islets identifies T1D-associated genes and regulatory signals.

ABSTRACT: Genome-wide association studies (GWASs) have identified over 100 signals associated with type 1 diabetes (T1D). However, it has been challenging to translate any given T1D GWAS signal into mechanistic insights, such as causal variants, their target genes, and the specific cell types involved. Here, we present a comprehensive multi-omic integrative analysis of single-cell/nucleus resolution profiles of gene expression and chromatin accessibility in human pancreatic islets under baseline and T1D-stimulating conditions. We nominate effector cell types for all T1D GWAS signals and the regulatory elements and genes for three independent T1D signals acting through β cells at the DLK1/MEG3, RASGRP1, and TOX loci. Subsequently, we validated the functional impact of these genes and regulatory regio

SUBMITTER: D'Oliveira Albanus R 

PROVIDER: S-EPMC12477748 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature