Cis-regulatory hubs: a new 3D model of complex disease genetics with an application to schizophrenia.

ABSTRACT: The 3D conformation of the chromatin creates complex networks of noncoding regulatory regions (distal elements) and promoters impacting gene regulation. Despite the importance of the role of noncoding regions in complex diseases, little is known about their interplay within regulatory hubs and implication in multigenic diseases such as schizophrenia. Here we show that cis-regulatory hubs (CRHs) in neurons highlight functional interactions between distal elements and promoters, providing a model to explain epigenetic mechanisms involved in complex diseases. CRHs represent a new 3D model, where distal elements interact to create a complex network of active genes. In a disease context, CRHs highlighted strong enrichments in schizophrenia-associated genes, schizophrenia-associated SNPs, and sc

SUBMITTER: Mangnier L 

PROVIDER: S-EPMC8807870 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature