International meta-analysis of PTSD genome-wide association studies identifies sex- and ancestry-specific genetic risk loci.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
08 10 2019
08 10 2019
Historique:
received:
25
07
2019
accepted:
18
09
2019
entrez:
10
10
2019
pubmed:
9
10
2019
medline:
20
2
2020
Statut:
epublish
Résumé
The risk of posttraumatic stress disorder (PTSD) following trauma is heritable, but robust common variants have yet to be identified. In a multi-ethnic cohort including over 30,000 PTSD cases and 170,000 controls we conduct a genome-wide association study of PTSD. We demonstrate SNP-based heritability estimates of 5-20%, varying by sex. Three genome-wide significant loci are identified, 2 in European and 1 in African-ancestry analyses. Analyses stratified by sex implicate 3 additional loci in men. Along with other novel genes and non-coding RNAs, a Parkinson's disease gene involved in dopamine regulation, PARK2, is associated with PTSD. Finally, we demonstrate that polygenic risk for PTSD is significantly predictive of re-experiencing symptoms in the Million Veteran Program dataset, although specific loci did not replicate. These results demonstrate the role of genetic variation in the biology of risk for PTSD and highlight the necessity of conducting sex-stratified analyses and expanding GWAS beyond European ancestry populations.
Identifiants
pubmed: 31594949
doi: 10.1038/s41467-019-12576-w
pii: 10.1038/s41467-019-12576-w
pmc: PMC6783435
doi:
Substances chimiques
Ubiquitin-Protein Ligases
EC 2.3.2.27
parkin protein
EC 2.3.2.27
Types de publication
Journal Article
Meta-Analysis
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
4558Subventions
Organisme : NIMHD NIH HHS
ID : R01 MD011728
Pays : United States
Organisme : NIMH NIH HHS
ID : F32 MH109274
Pays : United States
Organisme : NIMH NIH HHS
ID : R21 MH112956
Pays : United States
Organisme : Medical Research Council
ID : MR/L010305/1
Pays : United Kingdom
Organisme : RRD VA
ID : IK1 RX002325
Pays : United States
Organisme : BLRD VA
ID : I01 BX002558
Pays : United States
Organisme : NIMH NIH HHS
ID : U01 MH109536
Pays : United States
Organisme : NIMH NIH HHS
ID : T32 MH017119
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH106595
Pays : United States
Organisme : NIMH NIH HHS
ID : K01 MH118467
Pays : United States
Organisme : RRD VA
ID : IK2 RX002922
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH103291
Pays : United States
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