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Genetic predictors of hippocampal subfield volume in PTSD cases and trauma-exposed controls
- Source :
- European Journal of Psychotraumatology, article-version (VoR) Version of Record, European Journal of Psychotraumatology, Vol 11, Iss 1 (2020)
- Publication Year :
- 2020
-
Abstract
- Behavioural, structural, and functional neuroimaging have implicated the hippocampus as a critical brain region in posttraumatic stress disorder (PTSD) pathogenesis. Recent work in a normative, primarily European, sample identified 15 unique genetic loci contributing to structural variability in six hippocampal subfield volumes. We explored the relevance of these loci in two samples (Mental Illness Research Education and Clinical Centre [MIRECC] and Grady; n = 290) of trauma-exposed individuals enriched for PTSD and of diverse ancestry. Four of the previous loci demonstrated nominal evidence of replication in the MIRECC dataset, primarily within non-Hispanic whites (NHW). One locus replicated in the Grady cohort, which was composed exclusively of non-Hispanic blacks (NHB). Our data supported genetic interactions with diagnosis of lifetime PTSD and genetic interactions with childhood trauma in the MIRECC sample, but not the Grady sample. Given the racial, diagnostic, and trauma-exposure differences with the original genome-wide association study (GWAS) report, we conducted a full GWAS in the MIRECC and Grady datasets. Interactions between genetic variants and lifetime PTSD or childhood trauma were interrogated for single nucleotide polymorphisms (SNPs) with evidence of main effects. Genetic associations surpassed false discovery rate (FDR)-correction within hippocampal subfields in fimbria, subiculum, cornu ammonis-1 (CA1), and hippocampal amygdala transition area (HATA). One association was replicated in the Grady cohort (rs12880795 in TUNAR with left (L)-HATA volume). The most significant association in the MIRECC dataset was between rs6906714 in LINC02571 and right (R)-fimbria volume (p = 5.99×10−8, q = 0.0056). Interestingly, the effect of rs6906714 on R-fimbria volume increased with exposure to childhood trauma (gene*environment [G*E] interaction p = 0.022). These preliminary results argue for G*E interactions between genetic loci with PTSD and childhood trauma on hippocampal phenotypes. Our results underscore the need for larger neuroimaging-genetic studies in PTSD, trauma, and ancestrally diverse populations.
- Subjects :
- 050103 clinical psychology
hippocampus
hipocampo
RC435-571
TEPT
Hippocampus
Hippocampal formation
海马
Pathogenesis
03 medical and health sciences
0302 clinical medicine
Functional neuroimaging
subcampos hipocampales
Medicine
0501 psychology and cognitive sciences
genetics
• Gene by environment interactions of genetic loci with both PTSD and childhood trauma on hippocampal phenotypes
海马亚区
structural MRI
Psychiatry
childhood trauma
Basic Research Article
trauma infantil
business.industry
05 social sciences
Resonancia magnética estructural
PTSD
童年期创伤
genética
030227 psychiatry
hippocampal subfields
Posttraumatic stress
Brain region
结构性核磁共振
business
Neuroscience
Research Article
遗传学
Subjects
Details
- ISSN :
- 20008066 and 12880795
- Volume :
- 11
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- European journal of psychotraumatology
- Accession number :
- edsair.doi.dedup.....97d08bf4676eaf282c9b2c99adbb0eba