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

dc.contributor.author

Duncan, LE

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Ratanatharathorn, A

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Aiello, AE

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Almli, LM

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Amstadter, AB

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Ashley-Koch, AE

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Baker, DG

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Beckham, JC

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Bierut, LJ

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Bisson, J

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Bradley, B

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Chen, C-Y

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Dalvie, S

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Farrer, LA

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Galea, S

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Garrett, ME

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Gelernter, JE

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Guffanti, G

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Hauser, MA

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Johnson, EO

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Kessler, RC

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Kimbrel, NA

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King, A

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Koen, N

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Kranzler, HR

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Logue, MW

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Maihofer, AX

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Martin, AR

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Miller, MW

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Morey, RA

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Nugent, NR

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Rice, JP

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Ripke, S

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Roberts, AL

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Saccone, NL

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Smoller, JW

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Stein, DJ

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Stein, MB

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Sumner, JA

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Uddin, M

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Ursano, RJ

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Wildman, DE

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Yehuda, R

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Zhao, H

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Daly, MJ

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Liberzon, I

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Ressler, KJ

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Nievergelt, CM

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Koenen, KC

dc.coverage.spatial

England

dc.date.accessioned

2017-07-01T14:50:44Z

dc.date.available

2017-07-01T14:50:44Z

dc.date.issued

2017-04-25

dc.description.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.

dc.identifier

https://www.ncbi.nlm.nih.gov/pubmed/28439101

dc.identifier

mp201777

dc.identifier.eissn

1476-5578

dc.identifier.uri

https://hdl.handle.net/10161/14966

dc.language

eng

dc.publisher

Springer Science and Business Media LLC

dc.relation.ispartof

Mol Psychiatry

dc.relation.isversionof

10.1038/mp.2017.77

dc.title

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

dc.type

Journal article

duke.contributor.orcid

Ashley-Koch, AE|0000-0001-5409-9155

duke.contributor.orcid

Beckham, JC|0000-0001-8746-8949

duke.contributor.orcid

Kimbrel, NA|0000-0001-7218-1005

pubs.author-url

https://www.ncbi.nlm.nih.gov/pubmed/28439101

pubs.organisational-group

Clinical Science Departments

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Duke

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Duke Institute for Brain Sciences

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Duke Molecular Physiology Institute

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Duke-UNC Center for Brain Imaging and Analysis

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Institutes and Centers

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Institutes and Provost's Academic Units

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Psychiatry & Behavioral Sciences

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Psychiatry & Behavioral Sciences, Translational Neuroscience

pubs.organisational-group

School of Medicine

pubs.organisational-group

University Institutes and Centers

pubs.publication-status

Published online

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