Comprehensive exploration of the genetic contribution of the dopaminergic and serotonergic pathways to psychiatric disorders

Abstract

ABSTRACTPsychiatric disorders are highly prevalent and display considerable clinical and genetic overlap. Dopaminergic and serotonergic neurotransmission have been shown to have an important role in many psychiatric disorders. Here we aim to assess the genetic contribution of these systems to eight psychiatric disorders (ADHD, ANO, ASD, BIP, MD, OCD, SCZ and TS) using publicly available GWAS analyses performed by the Psychiatric Genomics Consortium. To do so, we elaborated four different gene sets using the Gene Ontology and KEGG pathways tools: two ‘wide’ selections for dopamine (DA) and for serotonin (SERT), and two ‘core’ selections for the same systems. At the gene level, we found 67 genes from the DA and/or SERT gene sets significantly associated with one of the studied disorders, and 12 of them were associated with two different disorders. Gene-set analysis revealed significant associations for ADHD and ASD with the wide DA gene set, for BIP with the wide SERT gene set, and for MD with both the core DA set and the core SERT set. Interestingly, interrogation of the cross-disorder GWAS meta-analysis displayed association with the wide DA gene set. To our knowledge, this is the first time that these two neurotransmitter systems have systematically been inspected in these disorders. Our results support a cross-disorder contribution of dopaminergic and serotonergic systems in several psychiatric conditions.