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

ABSTRACT: Genome wide association studies (GWAS) have identified over 100 signals associated with type 1 diabetes (T1D). However, translating any given T1D GWAS signal into mechanistic insights, including putative causal variants and the context (cell type and cell state) in which they function, has been limited. Here, we present a comprehensive multi-omic integrative analysis of single-cell/nucleus resolution profiles of gene expression and chromatin accessibility in healthy and autoantibody⁺ (AAB+) human islets, as well as islets under multiple T1D stimulatory conditions. We broadly nominate effector cell types for all T1D GWAS signals. We further nominated higher-resolution contexts, including effector cell types, regulatory elements, and genes for three independent T1D risk variants a

SUBMITTER: Zhao Z 

PROVIDER: S-EPMC10602166 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature