Largest GWAS of PTSD (N=20 070) yields genetic overlap with schizophrenia and sex differences in heritability.

Abstract

The Psychiatric Genomics Consortium-Posttraumatic Stress Disorder group (PGC-PTSD) combined genome-wide case-control molecular genetic data across 11 multiethnic studies to quantify PTSD heritability, to examine potential shared genetic risk with schizophrenia, bipolar disorder, and major depressive disorder and to identify risk loci for PTSD. Examining 20 730 individuals, we report a molecular genetics-based heritability estimate (h(2)SNP) for European-American females of 29% that is similar to h(2)SNP for schizophrenia and is substantially higher than h(2)SNP in European-American males (estimate not distinguishable from zero). We found strong evidence of overlapping genetic risk between PTSD and schizophrenia along with more modest evidence of overlap with bipolar and major depressive disorder. No single-nucleotide polymorphisms (SNPs) exceeded genome-wide significance in the transethnic (overall) meta-analysis and we do not replicate previously reported associations. Still, SNP-level summary statistics made available here afford the best-available molecular genetic index of PTSD-for both European- and African-American individuals-and can be used in polygenic risk prediction and genetic correlation studies of diverse phenotypes. Publication of summary statistics for ∼10 000 African Americans contributes to the broader goal of increased ancestral diversity in genomic data resources. In sum, the results demonstrate genetic influences on the development of PTSD, identify shared genetic risk between PTSD and other psychiatric disorders and highlight the importance of multiethnic/racial samples. As has been the case with schizophrenia and other complex genetic disorders, larger sample sizes are needed to identify specific risk loci.Molecular Psychiatry advance online publication, 25 April 2017; doi:10.1038/mp.2017.77.

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10.1038/mp.2017.77

Publication Info

Duncan, LE, A Ratanatharathorn, AE Aiello, LM Almli, AB Amstadter, AE Ashley-Koch, DG Baker, JC Beckham, et al. (2017). Largest GWAS of PTSD (N=20 070) yields genetic overlap with schizophrenia and sex differences in heritability. Mol Psychiatry. 10.1038/mp.2017.77 Retrieved from https://hdl.handle.net/10161/14966.

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Scholars@Duke

Ashley-Koch

Allison Elizabeth Ashley-Koch

Professor in Medicine

My work focuses on the dissection of human traits using multi-omic technologies (genetics, epigenetics, metabolomics and proteomics).  I am investigating the basis of several neurological and psychiatric conditions such as neural tube defects and post-traumatic stress disorder. I also study modifiers of sickle cell disease.

Beckham

Jean Crowell Beckham

Professor in Psychiatry and Behavioral Sciences

Interest in assessment and treatment of trauma, particularly as occurs for both women and men during military service; focus in treatment outcome of differential and collective contribution for psychopharmacological and behavioral interventions in PTSD populations; long term physical health effects of chronic posttraumatic stress disorder.

Hauser

Michael Arthur Hauser

Professor in Medicine

Dr. Hauser has a strong interest in ocular genetics. Genomic studies at the Center for Human Genetics have identified multiple linkage peaks and susceptibility genes in primary open angle glaucoma (POAG) and age related macular degeneration (AMD). Dr. Hauser has recently accepted a 20% appointment at the Singapore Eye Research INstitute and the Duke/National University of Singapore.  In collaboration with multiple collaborators in Singapore, and Dr. Rand Allingham at the Duke Eye Center, Dr. Hauser is currently conducting a genome wide association study for glaucoma in individuals of African ancestry. These investigations include large datasets collected in Ghana, Nigeria, and South Africa.  
 
Dr. Hauser is also involved in collaborative investigations into the genetics of post-tramatic stress disorder in US veterans from Iraq and Afghanistan.   Major collaborators include Dr. Allison Ashley Koch, Dr. Jean Beckham, Dr. Christine Marx and the MIRECC Collaborative group at the Durham Veteran's Administration.  We have published a genome wide association study, as well as numerous investigations into candidate genes.  Epigenomic DNA methylation analysis and gene expression analysis of 3500 individuals is currently ongoing. 

Kimbrel

Nathan Andrew Kimbrel

Associate Professor in Psychiatry and Behavioral Sciences

My primary areas of interest include the etiology, assessment, and treatment of PTSD, depression, suicide, and non-suicidal self-injury. I primarily work with veterans, firefighters, and emergency medical personnel due to their high levels of occupational exposure to traumatic stress. I also have long-standing interests in genetics, epigenetics, GxE research, personality, smoking, comorbidity, and statistical modeling procedures, such as CFA, SEM, and mixture modeling.

Morey

Rajendra A. Morey

Professor of Psychiatry and Behavioral Sciences

Research in my lab is focused on brain changes associated with posttraumatic stress disorder (PTSD), traumatic brain injury (TBI), and other neuropsychiatric disorders. We apply several advanced methods for understanding brain function including functional MRI, structural MRI, diffusion tensor imaging, and genetic effects.


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