Epistatic evidence for gender-dependant slow neurotransmission signalling in substance use disorders: PPP1R12B versus PPP1R1B.

ABSTRACT:

Background

Slow neurotransmission including DARPP-32 signalling is implicated in substance use disorders (SUDs) by experimental systems but not yet in the human aetiology. PPP1R12B, encoding another protein in the DARPP-32 family, hasn't been studied in the brain.

Methods

Brain-regional gene activity was assessed in three different animal models of SUDs for mRNA level alterations. Genetic associations were assessed by meta-analysis of pre-existing dbGaP GWAS datasets for main effects and epistasis with known genetic risks, followed by cell type-specific pathway delineation. Parkinson's disease (PD) was included as a dopamine-related disease control for SUDs.

Findings

In animal models of SUDs, environmentally-altered PPP1R12B expression sex-dependently involves motivat

SUBMITTER: Liu K 

PROVIDER: S-EPMC7581882 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature