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

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. ORCID: https://orcid.org/0000-0001-5170-1243, 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., Sumner, J. A., Uddin, M., Ursano, R. J., Wildman, D. E., Yehuda, Zhao, H., Daly, M. J., Liberzon, I., Ressler, K. J., Nievergelt, C. M. and Koenen, K. C. 2018. Largest GWAS of PTSD (N=20 070) yields genetic overlap with schizophrenia and sex differences in heritability. Molecular Psychiatry 23 , pp. 666-673. 10.1038/mp.2017.77

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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 (h2SNP) for European-American females of 29% that is similar to h2SNP for schizophrenia and is substantially higher than h2SNP 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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Subjects:	R Medicine > R Medicine (General)
Publisher:	Springer Nature
ISSN:	1359-4184
Date of First Compliant Deposit:	28 March 2017
Date of Acceptance:	15 February 2017
Last Modified:	05 May 2023 22:12
URI:	https://orca.cardiff.ac.uk/id/eprint/99406

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