title: Genome-wide association study identifies new susceptibility loci for posttraumatic stress disorder.
abstract: BACKGROUND
  Genetic factors influence the risk for posttraumatic stress disorder (PTSD), a potentially chronic and disabling psychiatric disorder that can arise after exposure to trauma. Candidate gene association studies have identified few genetic variants that contribute to PTSD risk.
  
  
  METHODS
  We conducted genome-wide association analyses in 1578 European Americans (EAs), including 300 PTSD cases, and 2766 African Americans, including 444 PTSD cases, to find novel common risk alleles for PTSD. We used the Illumina Omni1-Quad microarray, which yielded approximately 870,000 single nucleotide polymorphisms (SNPs) suitable for analysis.
  
  
  RESULTS
  In EAs, we observed that one SNP on chromosome 7p12, rs406001, exceeded genome-wide significance (p = 3.97 × 10(-8)). A SNP that maps to the first intron of the Tolloid-Like 1 gene (TLL1) showed the second strongest evidence of association, although no SNPs at this locus reached genome-wide significance. We then tested six SNPs in an independent sample of nearly 2000 EAs and successfully replicated the association findings for two SNPs in the first intron of TLL1, rs6812849 and rs7691872, with p values of 6.3 × 10(-6) and 2.3 × 10(-4), respectively. In the combined sample, rs6812849 had a p value of 3.1×10(-9). No significant signals were observed in the African American part of the sample. Genome-wide association study analyses restricted to trauma-exposed individuals yielded very similar results.
  
  
  CONCLUSIONS
  This study identified TLL1 as a new susceptibility gene for PTSD.
authors.affiliation: Departments of Genetics, Yale University School of Medicine, New Haven; Veterans Affairs Connecticut Healthcare Center, West Haven, Connecticut.
authors.forename: Pingxing
authors.initials: P
authors.lastname: Xie
authors.forename: Henry R
authors.initials: HR
authors.lastname: Kranzler
authors.forename: Can
authors.initials: C
authors.lastname: Yang
authors.forename: Hongyu
authors.initials: H
authors.lastname: Zhao
authors.forename: Lindsay A
authors.initials: LA
authors.lastname: Farrer
authors.forename: Joel
authors.initials: J
authors.lastname: Gelernter
mesh_terms: D000328:Adult; D001741:Black or African American / Q000235:genetics; D000483:Alleles; D016022:Case-Control Studies; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D013313:Stress Disorders, Post-Traumatic / Q000235:genetics*; D055394:Tolloid-Like Metalloproteinases / Q000235:genetics*; D044465:White People / Q000235:genetics
chemical_list: D055394:Tolloid-Like Metalloproteinases; C484478:TLL1 protein, human
keywords: American populations; TLL1; genome-wide association study; posttraumatic stress disorder