Elevated NEGR1 in brain induces anxiety or depression-like phenotypes and synaptic dysfunction.

ABSTRACT: Single nucleotide polymorphisms (SNPs) within 1p31.1 region have shown significant associations with depression, and our prior functional genomics pinpointed a regulatory variant rs3101339 among them. However, its precise role in depression pathogenesis remains elusive. In this study, we employed a series of analytical and functional approaches, including regulatory element annotation, brain expression quantitative trait loci (eQTL), reporter gene assay, electrophoretic mobility shift assay (EMSA), and precise genome editing. Our results confirmed that rs3101339 is a causal variant within 1p31.1 with its risk allele C upregulating NEGR1 expression. To further investigate the consequences of NEGR1 upregulation, we overexpressed NEGR1 in specific region of the mouse brain (including medial p

SUBMITTER: Zhang YQ 

PROVIDER: S-EPMC12436153 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature