Comprehensive exploration of the genetic contribution of the dopaminergic and serotonergic pathways to psychiatric disorders.
Journal
Translational psychiatry
ISSN: 2158-3188
Titre abrégé: Transl Psychiatry
Pays: United States
ID NLM: 101562664
Informations de publication
Date de publication:
10 01 2022
10 01 2022
Historique:
received:
07
01
2021
accepted:
13
10
2021
revised:
08
09
2021
entrez:
11
1
2022
pubmed:
12
1
2022
medline:
1
2
2022
Statut:
epublish
Résumé
Psychiatric disorders are highly prevalent and display considerable clinical and genetic overlap. Dopaminergic and serotonergic neurotransmission have been shown to play an important role in many psychiatric disorders. Here we aim to assess the genetic contribution of these systems to eight psychiatric disorders (attention-deficit hyperactivity disorder (ADHD), anorexia nervosa (ANO), autism spectrum disorder (ASD), bipolar disorder (BIP), major depression (MD), obsessive-compulsive disorder (OCD), schizophrenia (SCZ) and Tourette's syndrome (TS)) using publicly available GWAS analyses performed by the Psychiatric Genomics Consortium that include more than 160,000 cases and 275,000 controls. To do so, we elaborated four different gene sets: two 'wide' selections for dopamine (DA) and for serotonin (SERT) using the Gene Ontology and KEGG pathways tools, and two'core' selections for the same systems, manually curated. 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 the core SERT set. Interestingly, interrogation of a cross-disorder GWAS meta-analysis of the eight psychiatric conditions displayed association with the wide DA gene set. To our knowledge, this is the first systematic examination of genes encoding proteins essential to the function of these two neurotransmitter systems in these disorders. Our results support a pleiotropic contribution of the dopaminergic and serotonergic systems in several psychiatric conditions.
Identifiants
pubmed: 35013130
doi: 10.1038/s41398-021-01771-3
pii: 10.1038/s41398-021-01771-3
pmc: PMC8748838
doi:
Substances chimiques
Dopamine
VTD58H1Z2X
Types de publication
Journal Article
Meta-Analysis
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
11Informations de copyright
© 2021. The Author(s).
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