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Cited by 425Posttraumatic Stress Disorder ResearchGenetic Associations and EpidemiologySchizophrenia research and treatment

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

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Duncan, L E, Ratanatharathorn, A, Aiello, A E, Almli, L M, Amstadter, A B, Ashley-Koch, A E, Baker, D G, Beckham, J C +41 more·2018·Molecular Psychiatry
DOI 10.1038/mp.2017.77PMC PMC5696105
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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.

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  • Multi-ethnic work has been slow in most disease areas, limiting even the opportunity to assess PRS in non-European cohorts.

    “So far, multi-ethnic work has been slow in most disease areas54, limiting even the opportunity to assess PRS in non-European cohorts.”

    From Clinical use of current polygenic risk scores may exacerbate health disparities (2019) · cites this paper as [54]

    The Discussion says that external data resources needed for PRS are far less common for non-European populations and nonexistent for many, supporting the claimed limitation on assessing PRS. It does not establish that multi-ethnic work has been slow in most disease areas; that scope goes beyond what this PTSD paper states. (LLM, conf=0.82)

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Authors
Duncan, L. E., Ratanatharathorn, A., Aiello, A. E., Almli, L. M., Amstadter, A. B., Ashley-Koch, A. E., Baker, D. G., Beckham, J. C., Bierut, L. J., Bisson, J., Bradley, B., Chen, C.-Y., Dalvie, S., Farrer, L. A., Galea, S., Garrett, M. E., Gelernter, J. E., Guffanti, G., Hauser, M. A., Johnson, E. O., Kessler, R. C., Kimbrel, N. A., King, A., Koen, N., Kranzler, H. R., Logue, M. W., Maihofer, A. X., Martin, A. R., Miller, M. W., Morey, R. A., Nugent, N. R., Rice, J. P., Ripke, S., Roberts, A. L., Saccone, N. L., Smoller, J. W., Stein, D. J., Stein, M. B., Sumner, J. A., Uddin, M., Ursano, R. J., Wildman, D. E., Yehuda, R., Zhao, H., Daly, M. J., Liberzon, I., Ressler, K. J., Nievergelt, C. M., & Koenen, K. C.
Affiliations
  • Broad Institute (US)
  • Columbia University (US)
  • University of North Carolina at Chapel Hill (US)
  • Emory University (US)
  • Virginia Commonwealth University (US)
  • University of California San Diego (US)
  • Durham VA Health Care System (US)
  • Washington University in St. Louis (US)
  • Cardiff University (GB)
  • Harvard University (US)
  • University of Cape Town (ZA)
  • Boston University (US)
  • Yale University (US)
  • Duke University (US)
  • RTI International (US)
  • University of Michigan (US)
  • University of Pennsylvania (US)
  • Duke Medical Center (US)
  • Brown University (US)
  • Columbia University Irving Medical Center (US)
  • University of Illinois Urbana-Champaign (US)
  • Uniformed Services University of the Health Sciences (US)
  • James J. Peters VA Medical Center (US)
Corresponding author
  • Duncan, L E
  • Koenen, K C
ORCID
Venue
Molecular Psychiatry
Publisher
Springer Science and Business Media LLC
Published
2017-04-25
Volume
23
Issue
3
Pages
666-673
ISSN
  • 1359-4184 (ISSN-L)
  • 1476-5578
DOI
10.1038/mp.2017.77
PMC
PMC5696105
OpenAlex
W2610359325
Cited by
425
References
62
Citations by year
2026: 11 · 2025: 30 · 2024: 32 · 2023: 38 · 2022: 65 · 2021: 57 · 2020: 49 · 2019: 69 · 2018: 56 · 2017: 16 · 2016: 1
FWCI
7.93
Type
journal article
Language
en
Open access
Licence
Locations
  • Molecular Psychiatry (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • ORCA Online Research @Cardiff (Cardiff University) (acceptedVersion)
  • Digital Commons@Becker (Washington University School of Medicine) (submittedVersion, cc-by-nc-nd)
  • Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
  • DukeSpace (Duke University) (submittedVersion, cc-by-nc-nd)
  • eScholarship (California Digital Library) (submittedVersion)
  • eScholarship (California Digital Library) (submittedVersion, cc-by-nc-nd)
  • Refubium (Universitätsbibliothek der Freien Universität Berlin) (submittedVersion, cc-by-nc-nd)
  • Universitätsbibliothek der FU Berlin Hochschulschriftenstelle u. Dokumentenserver
  • UNC Libraries
Funders
  • Howard Hughes Medical Institute
  • U.S. Department of Veterans Affairs (I01 BX002150, I01 CX000431)
  • Harvard University
  • Sunovion
  • National Alliance for Research on Schizophrenia and Depression
  • Cohen Veterans Bioscience
  • One Mind
  • National Institutes of Health (5u01mh094432-04)
  • Stanley Center for Psychiatric Research, Broad Institute
  • Laureate Institute for Brain Research, University of Tulsa
  • National Institute of Mental Health (U01MH109539, U01 MH094432, U01MH109536, R01MH079806, K24MH094614, R01MH106595, R01MH111671)
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (P2CHD050924)
Topics
  • Social Sciences › Psychology › Clinical Psychology › Posttraumatic Stress Disorder Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
  • Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
Keywords
post-traumatic stress disorder, schizophrenia, bipolar disorder, major depressive disorder, genetic correlation, polygenic risk prediction, genetic susceptibility loci, African Americans, European Americans, psychiatric genetics
MeSH terms
Adult, Bipolar Disorder, Black or African American, Major Depressive Disorder, Depressive Disorder, Major, Female, Humans, Male, Middle Aged, Risk Factors, Schizophrenia, Sex Characteristics, Sex Factors, Stress Disorders, Post-Traumatic, Case-Control Studies, Genetic Predisposition to Disease, Multifactorial Inheritance, Polymorphism, Single Nucleotide, White People, Genome-Wide Association Study

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