Genome-wide association analyses identify 95 risk loci and provide insights into the neurobiology of post-traumatic stress disorder

Authors

Caroline M. Nievergelt, University of California, San Diego
Adam X. Maihofer, University of California, San Diego
Elizabeth G. Atkinson, Baylor College of Medicine
Chia Yen Chen, Biogen Inc.
Karmel W. Choi, Harvard T.H. Chan School of Public Health
Jonathan R.I. Coleman, South London and Maudsley NHS Foundation Trust
Nikolaos P. Daskalakis, Broad Institute
Laramie E. Duncan, Stanford University
Renato Polimanti, VA Connecticut Healthcare System
Cindy Aaronson, Icahn School of Medicine at Mount Sinai
Ananda B. Amstadter, Virginia Institute for Psychiatric and Behavioral Genetics
Soren B. Andersen, Research and Knowledge Centre
Ole A. Andreassen, Oslo Universitetssykehus
Paul A. Arbisi, VA Midwest Health Care Network
Allison E. Ashley-Koch, Duke University School of Medicine
S. Bryn Austin, Boston Children's Hospital
Esmina Avdibegoviç, University Clinical Center Tuzla
Dragan Babić, University Clinical Hospital Mostar
Silviu Alin Bacanu, VCU School of Medicine
Dewleen G. Baker, University of California, San Diego
Anthony Batzler, Mayo Clinic
Jean C. Beckham, Duke University School of Medicine
Sintia Belangero, Universidade Federal de São Paulo
Corina Benjet, Center for Global Mental Health
Carisa Bergner, Medical College of Wisconsin
Linda M. Bierer, VA Medical Center
Joanna M. Biernacka, Mayo Clinic
Laura J. Bierut, Washington University School of Medicine in St. Louis
Ariane Rung, LSU Health Sciences Center - New OrleansFollow
et al

Document Type

Article

Publication Date

4-18-2024

Publication Title

Nature Genetics

Abstract

Post-traumatic stress disorder (PTSD) genetics are characterized by lower discoverability than most other psychiatric disorders. The contribution to biological understanding from previous genetic studies has thus been limited. We performed a multi-ancestry meta-analysis of genome-wide association studies across 1,222,882 individuals of European ancestry (137,136 cases) and 58,051 admixed individuals with African and Native American ancestry (13,624 cases). We identified 95 genome-wide significant loci (80 new). Convergent multi-omic approaches identified 43 potential causal genes, broadly classified as neurotransmitter and ion channel synaptic modulators (for example, GRIA1, GRM8 and CACNA1E), developmental, axon guidance and transcription factors (for example, FOXP2, EFNA5 and DCC), synaptic structure and function genes (for example, PCLO, NCAM1 and PDE4B) and endocrine or immune regulators (for example, ESR1, TRAF3 and TANK). Additional top genes influence stress, immune, fear and threat-related processes, previously hypothesized to underlie PTSD neurobiology. These findings strengthen our understanding of neurobiological systems relevant to PTSD pathophysiology, while also opening new areas for investigation.

PubMed ID

38637617

Comments

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Recommended Citation

Nievergelt, Caroline M.; Maihofer, Adam X.; Atkinson, Elizabeth G.; Chen, Chia Yen; Choi, Karmel W.; Coleman, Jonathan R.I.; Daskalakis, Nikolaos P.; Duncan, Laramie E.; Polimanti, Renato; Aaronson, Cindy; Amstadter, Ananda B.; Andersen, Soren B.; Andreassen, Ole A.; Arbisi, Paul A.; Ashley-Koch, Allison E.; Austin, S. Bryn; Avdibegoviç, Esmina; Babić, Dragan; Bacanu, Silviu Alin; Baker, Dewleen G.; Batzler, Anthony; Beckham, Jean C.; Belangero, Sintia; Benjet, Corina; Bergner, Carisa; Bierer, Linda M.; Biernacka, Joanna M.; Bierut, Laura J.; Rung, Ariane; and al, et, "Genome-wide association analyses identify 95 risk loci and provide insights into the neurobiology of post-traumatic stress disorder" (2024). School of Public Health Faculty Publications. 390.
https://digitalscholar.lsuhsc.edu/soph_facpubs/390
10.1038/s41588-024-01707-9