Genome-wide association study identifies new susceptibility loci for posttraumatic stress disorder

Biol Psychiatry. 2013 Nov 1;74(9):656-63. doi: 10.1016/j.biopsych.2013.04.013. Epub 2013 May 28.

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.

Keywords: American populations; TLL1; genome-wide association study; posttraumatic stress disorder.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adult
  • African Americans / genetics
  • Alleles
  • Case-Control Studies
  • Chromosomes, Human, Pair 7 / genetics
  • European Continental Ancestry Group / genetics
  • Female
  • Genetic Predisposition to Disease / genetics*
  • Genome-Wide Association Study*
  • Humans
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • Stress Disorders, Post-Traumatic / genetics*
  • Tolloid-Like Metalloproteinases / genetics*

Substances

  • Tolloid-Like Metalloproteinases
  • TLL1 protein, human