title: Genetic association analysis of 300 genes identifies a risk haplotype in SLC18A2 for post-traumatic stress disorder in two independent samples.
abstract: The 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.
authors: 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.
authors: Nadia
authors: N
authors: Solovieff
authors: Department of Society, Human Development and Health, Harvard School of Public Health, Boston, MA, USA.
authors: Andrea L
authors: AL
authors: Roberts
authors: Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USA.
authors: Andrew
authors: A
authors: Ratanatharathorn
authors: Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USA.
authors: Michelle
authors: M
authors: Haloosim
authors: 1] Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA [2] Channing Division of Network Medicine, BWH, Harvard Medical School, Boston, MA, USA.
authors: Immaculata
authors: I
authors: De Vivo
authors: Mental Health Service, VA Ann Arbor Health Systems, MI, USA.
authors: Anthony P
authors: AP
authors: King
authors: 1] Mental Health Service, VA Ann Arbor Health Systems, MI, USA [2] Department of Psychiatry, University of Michigan Medical School, Ann Arbor, MI, USA.
authors: Israel
authors: I
authors: Liberzon
authors: Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor, MI, USA.
authors: Allison
authors: A
authors: Aiello
authors: 1] Center for Molecular Medicine and Genetics, Department of Psychiatry & Behavioral Neurosciences, Wayne State University School of Medicine, Detroit, MI, USA [2] Department of Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine, Detroit, MI, USA.
authors: Monica
authors: M
authors: Uddin
authors: 1] Center for Molecular Medicine and Genetics, Department of Psychiatry & Behavioral Neurosciences, Wayne State University School of Medicine, Detroit, MI, USA [2] Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, USA.
authors: Derek E
authors: DE
authors: Wildman
authors: Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USA.
authors: Sandro
authors: S
authors: Galea
authors: 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.
authors: Jordan W
authors: JW
authors: Smoller
authors: 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 [4] Division of Psychiatric Genomics, Mount Sinai School of Medicine, New York, NY, USA.
authors: Shaun M
authors: SM
authors: Purcell
authors: Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USA.
authors: Karestan C
authors: KC
authors: Koenen
mesh_terms: D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D013313:Stress Disorders, Post-Traumatic / Q000235:genetics*; D050493:Vesicular Monoamine Transport Proteins / Q000235:genetics*
chemical_list: C493452:SLC18A2 protein, human; D050493:Vesicular Monoamine Transport Proteins