Genetic variants associated with psychotic symptoms across psychiatric disorders.
Adult
Bipolar Disorder
/ diagnosis
Calcium Channels, L-Type
/ genetics
Depressive Disorder, Major
/ diagnosis
Female
Genetic Variation
Genome-Wide Association Study
Humans
Male
Mental Disorders
/ diagnosis
Polymorphism, Single Nucleotide
Psychiatric Status Rating Scales
Schizophrenia
/ diagnosis
Young Adult
CACNA1C
Cross-disorder risk
Depression
Genetics
Schizophrenia
Symptom clusters
Journal
Neuroscience letters
ISSN: 1872-7972
Titre abrégé: Neurosci Lett
Pays: Ireland
ID NLM: 7600130
Informations de publication
Date de publication:
16 02 2020
16 02 2020
Historique:
received:
19
09
2019
revised:
06
12
2019
accepted:
11
01
2020
pubmed:
17
1
2020
medline:
17
4
2021
entrez:
17
1
2020
Statut:
ppublish
Résumé
Recent evidence suggests that psychiatric symptoms share a common genetic liability across diagnostic categories. The present study investigated the effects of variants within previously identified relevant genes on specific symptom clusters, independently from the diagnosis. 1550 subjects affected by Schizophrenia (SCZ), Major Depressive Disorder or Bipolar Disorder were included. Symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS) and the Hamilton Depression Rating Scale (HDRS). Principal component analysis and a further clinical refinement were used to define symptom clusters. Clusters scores were tested for association with 46 genetic variants within nine genes previously linked to one or more major psychiatric disorders by large genome wide association studies (ANK3, CACNA1C, CACNB2, FKBP5, FZD3, GRM7, ITIH3, SYNE1, TCF4). Exploratory analyses were performed in each disorder separately to further elucidate the SNPs effects. five PANSS clusters (Negative; Impulsiveness; Cognitive; Psychotic; Depressive) and four HDRS clusters (Core Depressive; Somatic; Psychotic-like; Insomnia) were identified. CACNA1C rs11615998 was associated with HDRS Psychotic cluster in the whole sample. In the SCZ sample, CACNA1C rs11062296 was associated with PANSS Impulsiveness cluster and CACNA1C rs2238062 was associated with PANSS negative cluster. CACNA1C rs11615998 was associated with psychotic symptoms (C-allele carriers have decreased psychotic-risk) independently from the diagnosis, in line with the evidence of a cross disorder effect of many risk variants. This gene was previously associated with SCZ and cross-disorder liability to psychiatric disorders. Our findings confirmed that deep phenotyping is pivotal to clarify the role of genetic variants on symptoms patterns.
Sections du résumé
BACKGROUND
Recent evidence suggests that psychiatric symptoms share a common genetic liability across diagnostic categories. The present study investigated the effects of variants within previously identified relevant genes on specific symptom clusters, independently from the diagnosis.
METHODS
1550 subjects affected by Schizophrenia (SCZ), Major Depressive Disorder or Bipolar Disorder were included. Symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS) and the Hamilton Depression Rating Scale (HDRS). Principal component analysis and a further clinical refinement were used to define symptom clusters. Clusters scores were tested for association with 46 genetic variants within nine genes previously linked to one or more major psychiatric disorders by large genome wide association studies (ANK3, CACNA1C, CACNB2, FKBP5, FZD3, GRM7, ITIH3, SYNE1, TCF4). Exploratory analyses were performed in each disorder separately to further elucidate the SNPs effects.
RESULTS
five PANSS clusters (Negative; Impulsiveness; Cognitive; Psychotic; Depressive) and four HDRS clusters (Core Depressive; Somatic; Psychotic-like; Insomnia) were identified. CACNA1C rs11615998 was associated with HDRS Psychotic cluster in the whole sample. In the SCZ sample, CACNA1C rs11062296 was associated with PANSS Impulsiveness cluster and CACNA1C rs2238062 was associated with PANSS negative cluster.
DISCUSSION
CACNA1C rs11615998 was associated with psychotic symptoms (C-allele carriers have decreased psychotic-risk) independently from the diagnosis, in line with the evidence of a cross disorder effect of many risk variants. This gene was previously associated with SCZ and cross-disorder liability to psychiatric disorders. Our findings confirmed that deep phenotyping is pivotal to clarify the role of genetic variants on symptoms patterns.
Identifiants
pubmed: 31945448
pii: S0304-3940(20)30024-0
doi: 10.1016/j.neulet.2020.134754
pii:
doi:
Substances chimiques
CACNA1C protein, human
0
Calcium Channels, L-Type
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
134754Informations de copyright
Copyright © 2020 Elsevier B.V. All rights reserved.