Sex Significantly Impacts the Function of Major Depression-Linked Variants In Vivo.

ABSTRACT:

Background

Genome-wide association studies have discovered blocks of common variants-likely transcriptional-regulatory-associated with major depressive disorder (MDD), though the functional subset and their biological impacts remain unknown. Likewise, why depression occurs in females more frequently than males is unclear. We therefore tested the hypothesis that risk-associated functional variants interact with sex and produce greater impact in female brains.

Methods

We developed techniques to directly measure regulatory variant activity and sex interactions using massively parallel reporter assays in the mouse brain in vivo, in a cell type-specific manner, and applied these approaches to measure activity of >1000 variants from >30 MDD loci.

Results

We identified exten

SUBMITTER: Mulvey B 

PROVIDER: S-EPMC10425576 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature