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The pleiotropic contribution of genes in dopaminergic and serotonergic pathways to addiction and related behavioral traits

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Introduction: Co-occurrence of substance use disorders (SUD) and other behavioral  conditions, such as stress-related, aggressive or risk-taking behaviors, in the same  individual has been frequently described. As dopamine (DA) and serotonin (5-HT) have  been previously identified as key neurotransmitters for some of these phenotypes,  we explored the genetic contribution of these pathways to SUD and these comorbid  phenotypes in order to better understand the genetic relationship between them.  Methods: We tested the association of 275 dopaminergic genes and 176  serotonergic genes with these phenotypes by performing gene-based, gene-set  and transcriptome-wide association studies in 11 genome-wide association studies  (GWAS) datasets on SUD and related behaviors.  Results: At the gene-wide level, 68 DA and 27 5-HT genes were found to be associated  with at least one GWAS on SUD or related behavior. Among them, six genes had a  pleiotropic effect, being associated with at least three phenotypes: ADH1C, ARNTL,  CHRNA3, HPRT1, HTR1B and DRD2. Additionally, we found nominal associations  between the DA gene sets and SUD, opioid use disorder, antisocial behavior, irritability  and neuroticism, and between the 5-HT-core gene set and neuroticism. Predicted  gene expression correlates in brain were also found for 19 DA or 5-HT genes.  Discussion: Our study shows a pleiotropic contribution of dopaminergic and  serotonergic genes to addiction and related behaviors such as anxiety, irritability,  neuroticism and risk-taking behavior, highlighting a role for DA genes, which could  explain, in part, the co-occurrence of these phenotypes

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Frontiers In Psychiatry, 2023, vol. 14, p. 1-11

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cc-by (c)  Antón-Galindo, A. et al., 2023

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Articles publicats en revistes (Genètica, Microbiologia i Estadística)

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The pleiotropic contribution of genes in dopaminergic and serotonergic pathways to addiction and related behavioral traits