Largest GWAS of PTSD (N=20,070) Yields Genetic Overlap with Schizophrenia and Sex Differences in Heritability

By L. Duncan, A. Ratanatharathorn, Allison Aiello, L. Almli, A. Amstadter, A. Ashley-Koch, D. Baker, Jean C. Beckham, L. Bierut, J. Bisson and 39 more. 2017

392 citations recorded by the source corpus.

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.

Subfields: Clinical Psychology, Genetics, Social Psychology

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Clinical Psychology

1. Murray B. Stein
2. L. Duncan
3. Ronald C. Kessler
4. J. Su
5. Matthew K. Nock
6. Mustafa Sarkar
7. D. Fletcher

In Genetics

1. Chia-Yen Chen
2. Alicia R. Martin
3. L. Duncan
4. Patrick F. Sullivan
5. Jordan W. Smoller
6. Eli A. Stahl

In Social Psychology

1. Murray B. Stein
2. Ronald C. Kessler
3. J. Su
4. N. Sampson
5. Alan M. Zaslavsky
6. Philip S. Wang
7. Matthew K. Nock

Citations in the corpus

• Genome-wide association studies in ancestrally diverse populations: opportunities, methods, pitfalls, and recommendations. (2019, methodology): “For the ​stratified meta-analysis approach​, the QC criteria affected by allele frequencies can be applied to each population separately (​Supplemental Figure S1​) ​(Duncan et al., 2018; Peterson et al., 2017; Walters et al., 2018)​.”
• The Army Study to Assess Risk and Resilience in Servicemembers (Army STARRS): progress toward understanding suicide among soldiers (2018, background): “Results from this study are currently being shared with the Psychiatric Genomic Consortium PTSD Group [61] and will become part of future metaanalyses.”