Concordance of genetic variation that increases risk for anxiety disorders and posttraumatic stress disorders and that influences their underlying neurocircuitry.
Amygdala
/ diagnostic imaging
Anxiety Disorders
/ genetics
Brain
/ diagnostic imaging
Female
Genetic Predisposition to Disease
Genetic Variation
/ genetics
Genome-Wide Association Study
Humans
Linkage Disequilibrium
Male
Neural Pathways
/ physiopathology
Polymorphism, Single Nucleotide
/ genetics
Risk Factors
Stress Disorders, Post-Traumatic
/ genetics
Anxiety disorders
GWAS
Genetic concordance
PTSD
Subcortical brain structures
Journal
Journal of affective disorders
ISSN: 1573-2517
Titre abrégé: J Affect Disord
Pays: Netherlands
ID NLM: 7906073
Informations de publication
Date de publication:
15 02 2019
15 02 2019
Historique:
received:
31
05
2018
revised:
02
11
2018
accepted:
11
11
2018
entrez:
1
2
2019
pubmed:
1
2
2019
medline:
2
4
2019
Statut:
ppublish
Résumé
There have been considerable recent advances in understanding the genetic architecture of anxiety disorders and posttraumatic stress disorder (PTSD), as well as the underlying neurocircuitry of these disorders. However, there is little work on the concordance of genetic variations that increase risk for these conditions, and that influence subcortical brain structures. We undertook a genome-wide investigation of the overlap between the genetic influences from single nucleotide polymorphisms (SNPs) on volumes of subcortical brain structures and genetic risk for anxiety disorders and PTSD. We obtained summary statistics of genome-wide association studies (GWAS) of anxiety disorders (N For anxiety disorders, we found evidence of significant concordance between increased anxiety risk variants and variants associated with smaller amygdala volume. Further, by conditioning on brain volume GWAS, we identified novel variants that associate with smaller brain volumes and increase risk for disorders: rs56242606 was found to increase risk for anxiety disorders, while two variants (rs6470292 and rs683250) increase risk for PTSD, when conditioning on the GWAS of putamen volume. Despite using the largest available GWAS summary statistics, the analyses were limited by sample size. These preliminary data indicate that there is genome wide concordance between genetic risk factors for anxiety disorders and those for smaller amygdala volume, which is consistent with research that supports the involvement of the amygdala in anxiety disorders. It is notable that a genetic variant that contributes to both reduced putamen volume and PTSD plays a key role in the glutamatergic system. Further work with GWAS summary statistics from larger samples, and a more extensive look at the genetics underlying brain circuits, is needed to fully delineate the genetic architecture of these disorders and their underlying neurocircuitry.
Sections du résumé
BACKGROUND
There have been considerable recent advances in understanding the genetic architecture of anxiety disorders and posttraumatic stress disorder (PTSD), as well as the underlying neurocircuitry of these disorders. However, there is little work on the concordance of genetic variations that increase risk for these conditions, and that influence subcortical brain structures. We undertook a genome-wide investigation of the overlap between the genetic influences from single nucleotide polymorphisms (SNPs) on volumes of subcortical brain structures and genetic risk for anxiety disorders and PTSD.
METHOD
We obtained summary statistics of genome-wide association studies (GWAS) of anxiety disorders (N
RESULTS
For anxiety disorders, we found evidence of significant concordance between increased anxiety risk variants and variants associated with smaller amygdala volume. Further, by conditioning on brain volume GWAS, we identified novel variants that associate with smaller brain volumes and increase risk for disorders: rs56242606 was found to increase risk for anxiety disorders, while two variants (rs6470292 and rs683250) increase risk for PTSD, when conditioning on the GWAS of putamen volume.
LIMITATIONS
Despite using the largest available GWAS summary statistics, the analyses were limited by sample size.
CONCLUSIONS
These preliminary data indicate that there is genome wide concordance between genetic risk factors for anxiety disorders and those for smaller amygdala volume, which is consistent with research that supports the involvement of the amygdala in anxiety disorders. It is notable that a genetic variant that contributes to both reduced putamen volume and PTSD plays a key role in the glutamatergic system. Further work with GWAS summary statistics from larger samples, and a more extensive look at the genetics underlying brain circuits, is needed to fully delineate the genetic architecture of these disorders and their underlying neurocircuitry.
Identifiants
pubmed: 30699873
pii: S0165-0327(18)31178-9
doi: 10.1016/j.jad.2018.11.082
pmc: PMC6519055
mid: NIHMS1514282
pii:
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
885-896Subventions
Organisme : NIMH NIH HHS
ID : R01 MH117601
Pays : United States
Organisme : NIMH NIH HHS
ID : U01 MH109536
Pays : United States
Organisme : NIBIB NIH HHS
ID : U54 EB020403
Pays : United States
Informations de copyright
Copyright © 2018 Elsevier B.V. All rights reserved.
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