Genome-Wide Association Study of Post-Traumatic Stress Disorder in Two High-Risk Populations

Twin Res Hum Genet. 2017 Jun;20(3):197-207. doi: 10.1017/thg.2017.12. Epub 2017 Mar 6.

Abstract

Mexican Americans (MAs) and American Indians (AIs) constitute conspicuously understudied groups with respect to risk for post-traumatic stress disorder (PTSD), especially in light of findings showing racial/ethnic differences in trauma exposure and risk for PTSD. The purpose of this study was to examine genetic influences on PTSD in two minority cohorts. A genome-wide association study (GWAS) with sum PTSD symptoms for trauma-exposed subjects was run in each cohort. Six highly correlated variants in olfactory receptor family 11 subfamily L member 1 (OR11L1) were suggestively associated with PTSD in the MA cohort. These associations remained suggestively significant after permutation testing. A signal in a nearby olfactory receptor on chromosome 1, olfactory receptor family 2 subfamily L member 13 (OR2L13), tagged by rs151319968, was nominally associated with PTSD in the AI sample. Although no variants were significantly associated after correction for multiple testing in a meta-analysis of the two cohorts, pathway analysis of the top hits showed an enrichment cluster of terms related to sensory transduction, olfactory receptor activity, G-protein coupled receptors, and membrane. As previous studies have proposed a role for olfaction in PTSD, our results indicate this influence may be partially driven by genetic variation in the olfactory system.

Keywords: American Indians; GWAS; Mexican Americans; PTSD; enrichment analysis; olfaction.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Adult
  • Diseases in Twins / genetics
  • Female
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study*
  • Humans
  • Indians, North American / genetics
  • Male
  • Mexican Americans / genetics
  • Polymorphism, Single Nucleotide
  • Receptors, Odorant / genetics*
  • Risk Factors
  • Stress Disorders, Post-Traumatic / genetics*
  • Stress Disorders, Post-Traumatic / pathology

Substances

  • OR2W3 protein, human
  • Receptors, Odorant