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

Caroline M Nievergelt; Adam X Maihofer; Elizabeth G Atkinson; Chia-Yen Chen; Karmel W Choi; Jonathan R I Coleman; Nikolaos P Daskalakis; Laramie E Duncan; Renato Polimanti; Cindy Aaronson; See article text for complete list of authors; Ross Young

doi:10.1038/s41588-024-01707-9

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

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

Caroline M Nievergelt, Adam X Maihofer, Elizabeth G Atkinson, Chia-Yen Chen, Karmel W Choi, Jonathan R I Coleman, Nikolaos P Daskalakis, Laramie E Duncan, Renato Polimanti, Cindy Aaronson, …

Nature Genetics, Vol.56, pp.792-808

2024

DOI: https://doi.org/10.1038/s41588-024-01707-9

Abstract

genome-wide association studies

psychiatric disorders

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. © This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2024.

Details

Title: Genome-wide association analyses identify 95 risk loci and provide insights into the neurobiology of post-traumatic stress disorder
Authors: Caroline M Nievergelt (Corresponding Author) - University of California, San Diego
Adam X Maihofer - University of California, San Diego
Elizabeth G Atkinson - Baylor College of Medicine
Chia-Yen Chen - Harvard T.H. Chan School of Public Health
Karmel W Choi - Harvard T.H. Chan School of Public Health
Jonathan R I Coleman - King's College London
Nikolaos P Daskalakis - Harvard Medical School
Laramie E Duncan - Stanford University
Renato Polimanti - Yale University
Cindy Aaronson - Icahn School of Medicine at Mount Sinai
See article text for complete list of authors (Author)
Ross Young - University of the Sunshine Coast, Queensland, Office of the Deputy Vice-Chancellor (Research and Innovation)
Publication details: Nature Genetics, Vol.56, pp.792-808
Publisher: Nature Publishing Group
DOI: 10.1038/s41588-024-01707-9
ISSN: 1546-1718
Data Availability: Summary statistics for PGC-PTSD Freeze 3 will be made available upon publication under the accession ID ptsd2024 via the PGC website (https://pgc.unc.edu/for-researchers/download-results/). Access to study-level summary statistics and genotype data can be applied by using the PGC data access portal (https://pgc.unc.edu/for-researchers/data-access-committee/data-access-portal/).
Organisation Unit: Office of the Deputy Vice-Chancellor (Research and Innovation)
Language: English
Record Identifier: 991024895402621
Output Type: Journal article