• Nadia Solovieff, Andrea L Roberts, Andrew Ratanatharathorn, Michelle Haloosim, Immaculata De Vivo, Anthony P King, Israel Liberzon, Allison Aiello, Monica Uddin, Derek E Wildman, Sandro Galea, Jordan W Smoller, Shaun M Purcell, and Karestan C Koenen.
• 1] Department of Center of Human Genetics Research, Massachusetts General Hospital, Boston, MA, USA [2] Department of Stanley Center for Psychiatric Research, the Broad Institute of Harvard and MIT, Cambridge, MA, USA [3] Department of Psychiatry, Harvard Medical School, Boston, MA, USA.
• Neuropsychopharmacology. 2014 Jul 1;39(8):1872-9.

AbstractThe genetic architecture of post-traumatic stress disorder (PTSD) remains poorly understood with the vast majority of genetic association studies reporting on single candidate genes. We conducted a large genetic study in trauma-exposed European-American women (N=2538; 845 PTSD cases, 1693 controls) by testing 3742 SNPs across more than 300 genes and conducting polygenic analyses using results from the Psychiatric Genome-Wide Association Studies Consortium (PGC). We tested the association between each SNP and two measures of PTSD, a severity score and diagnosis. We found a significant association between PTSD (diagnosis) and SNPs (top SNP: rs363276, odds ratio (OR)=1.4, p=2.1E-05) in SLC18A2 (vesicular monoamine transporter 2). A haplotype analysis of 9 SNPs in SLC18A2, including rs363276, identified a risk haplotype (CGGCGGAAG, p=0.0046), and the same risk haplotype was associated with PTSD in an independent cohort of trauma-exposed African-Americans (p=0.049; N=748, men and women). SLC18A2 is involved in transporting monoamines to synaptic vesicles and has been implicated in a number of neuropsychiatric disorders including major depression. Eight genes previously associated with PTSD had SNPs with nominally significant associations (p<0.05). The polygenic analyses suggested that there are SNPs in common between PTSD severity and bipolar disorder. Our data are consistent with a genetic architecture for PTSD that is highly polygenic, influenced by numerous SNPs with weak effects, and may overlap with mood disorders. Genome-wide studies with very large samples sizes are needed to detect these types of effects.

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