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

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

Pingxing Xie  1 , Henry R Kranzler, Can Yang, Hongyu Zhao, Lindsay A Farrer, Joel Gelernter
Affiliations

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

Pingxing Xie et al. Biol Psychiatry. .

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.

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Conflict of interest statement

Dr. Kranzler has served as a consultant or advisory board member for Alkermes, Lilly, Lundbeck, Pfizer, and Roche. He is also a member of the American Society of Clinical Psychopharmacology’s Alcohol Clinical Trials Initiative, which is supported by Lilly, Lundbeck, Abbott, and Pfizer. The other authors report no biomedical financial interests or potential conflicts of interest.

Figures

Figure 1
Figure 1
Quintile-Quintile plots for whole cohort of European Americans (A), European Americans with trauma experiences (B), whole cohort of African Americans (C), and African Americans with trauma experiences (D). The genomic inflation factor (λ) is the ratio of the observed median p value to its expected value.
Figure 2
Figure 2
Regional Manhattan plots of the top two strongest association regions in European Americans: chromosome 7p12 (A) and chromosome 4q32 (B). The single nucleotide polymorphisms are color coded based on the linkage disequilibrium with the most significant single nucleotide polymorphism in each region, rs406001 and rs6812849, respectively.
See this image and copyright information in PMC

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