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Mol Psychiatry DOI:10.1038/mp.2017.77

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

Publication TypeJournal Article
Year of Publication2018
AuthorsDuncan, LE, Ratanatharathorn, A, Aiello, AE, Almli, LM, Amstadter, AB, Ashley-Koch, AE, Baker, DG, Beckham, JC, Bierut, LJ, Bisson, J, Bradley, B, Chen, C-Y, Dalvie, S, Farrer, LA, Galea, S, Garrett, ME, Gelernter, JE, Guffanti, G, Hauser, MA, Johnson, EO, Kessler, RC, Kimbrel, NA, King, A, Koen, N, Kranzler, HR, Logue, MW, Maihofer, AX, Martin, AR, Miller, MW, Morey, RA, Nugent, NR, Rice, JP, Ripke, S, Roberts, AL, Saccone, NL, Smoller, JW, Stein, DJ, Stein, MB, Sumner, JA, Uddin, M, Ursano, RJ, Wildman, DE, Yehuda, R, Zhao, H, Daly, MJ, Liberzon, I, Ressler, KJ, Nievergelt, CM, Koenen, KC
JournalMol Psychiatry
Date Published2018 03
KeywordsAdult, African Americans, Bipolar Disorder, Case-Control Studies, Depressive Disorder, Major, European Continental Ancestry Group, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Male, Middle Aged, Multifactorial Inheritance, Polymorphism, Single Nucleotide, Risk Factors, Schizophrenia, Sex Characteristics, Sex Factors, Stress Disorders, Post-Traumatic

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) for European-American females of 29% that is similar to h for schizophrenia and is substantially higher than h 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.


Alternate JournalMol. Psychiatry
PubMed ID28439101
PubMed Central IDPMC5696105
Grant ListK24 MH094614 / MH / NIMH NIH HHS / United States
R01 MH111671 / MH / NIMH NIH HHS / United States
I01 BX002150 / BX / BLRD VA / United States
U01 MH109536 / MH / NIMH NIH HHS / United States
I01 CX000431 / CX / CSRD VA / United States
U01 MH109539 / MH / NIMH NIH HHS / United States
R01 MH106595 / MH / NIMH NIH HHS / United States
U01 MH094432 / MH / NIMH NIH HHS / United States
P2C HD050924 / HD / NICHD NIH HHS / United States
K23 MH112852 / MH / NIMH NIH HHS / United States
R01 MH079806 / MH / NIMH NIH HHS / United States