title: Genome-Wide Association Study of Post-Traumatic Stress Disorder in Two High-Risk Populations.
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.
authors.affiliation: Department of Neuroscience,The Scripps Research Institute,La Jolla,CA,USA.
authors.forename: Whitney E
authors.initials: WE
authors.lastname: Melroy-Greif
authors.affiliation: Department of Genetics and Neurology,University of North Carolina,Chapel Hill,NC,USA.
authors.forename: Kirk C
authors.initials: KC
authors.lastname: Wilhelmsen
authors.affiliation: James J. Peters Veterans Affairs Medical Center and Traumatic Stress Studies Division,Psychiatry Department,Mount Sinai School of Medicine,New York City,NY,USA.
authors.forename: Rachel
authors.initials: R
authors.lastname: Yehuda
authors.affiliation: Department of Neuroscience,The Scripps Research Institute,La Jolla,CA,USA.
authors.forename: Cindy L
authors.initials: CL
authors.lastname: Ehlers
mesh_terms: D000293:Adolescent; D000328:Adult; D004200:Diseases in Twins / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D007198:Indians, North American / Q000235:genetics; D008297:Male; D017058:Mexican Americans / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D018035:Receptors, Odorant / Q000235:genetics*; D012307:Risk Factors; D013313:Stress Disorders, Post-Traumatic / Q000235:genetics* / Q000473:pathology
chemical_list: C000601325:OR2W3 protein, human; D018035:Receptors, Odorant
keywords: American Indians; GWAS; Mexican Americans; PTSD; enrichment analysis; olfaction