A Genome-Wide Identified Risk Variant for PTSD is a Methylation Quantitative Trait Locus and Confers Decreased Cortical Activation to Fearful Faces

Abstract

Genetic factors appear to be highly relevant to predicting differential risk for the development of post-traumatic stress disorder (PTSD). In a discovery sample, we conducted a genome- wide association study (GWAS) for PTSD using a small military cohort (Systems Biology PTSD Biomarkers Consortium; SBPBC, N=147) that was designed as a case-controlled sample of highly exposed, recently returning veterans with and without combat-related PTSD. A genome-wide significant single nucleotide polymorphism (SNP), rs717947, at chromosome 4p15 (N=147, b=31.34, P=1.28^10 -8) was found to associate with the gold-standard diagnostic measure for PTSD (the Clinician Administered PTSD Scale). We conducted replication and follow-up studies in an external sample, a larger urban community cohort (Grady Trauma Project, GTP, N=2006), to determine the robustness and putative functionality of this risk variant. In the GTP replication sample, SNP rs717947 associated with PTSD diagnosis in females (N=2006, P=0.005), but not males. SNP rs717947 was also found to be a methylation quantitative trait locus (meQTL) in the GTP replication sample (N=157, P=0.002). Further, the risk allele of rs717947 was associated with decreased medial and dorsolateral cortical activation to fearful faces (N=53, P<0.05) in the GTP replication sample. These data identify a genome-wide significant polymorphism conferring risk for PTSD, which was associated with differential epigenetic regulation and with differential cortical responses to fear in a replication sample. These results may provide new insight into understanding genetic and epigenetic regulation of PTSD and intermediate phenotypes that contribute to this disorder.

Open PDF

Document Details

Document Type
Technical Report
Publication Date
May 18, 2015
Accession Number
ADA621342

Entities

People

  • Alicia K. Smith
  • Duna Abu-amara
  • Janine Flory
  • Jennifer S. Stevens
  • Kristina B. Mercer
  • Lynn M. Almli
  • Qian Meng
  • Rasha Hammamieh
  • Ruoting Yang
  • Varun Kilaru

Organizations

  • U.S. Army Center for Environmental Health Research

Tags

Communities of Interest

  • Biomedical

DTIC Thesaurus Topics

  • Anxiety Disorders
  • Biology
  • Brain Injuries
  • Computational Biology
  • Diseases And Disorders
  • Genes
  • Genetic Phenomena
  • Genetic Structures
  • Genetics
  • Genome
  • Health Services
  • Medical Genetics
  • Phenotypes
  • Psychiatry
  • Systems Biology
  • Traumatic Stress Disorder

Fields of Study

  • Biology
  • Psychology

Readers

  • Molecular and genetic basis of cancer.
  • Neurotrauma and Rehabilitation Medicine.
  • Psychometric Testing or Psychological Assessment.

Technology Areas

  • Biotechnology