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; Ananda B Amstadter; Ole A Andreassen; Paul A Arbisi; Allison E Ashley-Koch; S Bryn Austin; Esmina Avdibegoviç; Dragan Babić; Silviu-Alin Bacanu; Dewleen G Baker; Anthony Batzler; Jean C Beckham; Sintia Belangero; Corina Benjet; AURORA Study

doi:10.1038/s41588-024-01707-9

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, Ananda B Amstadter, Ole A Andreassen, Paul A Arbisi, Allison E Ashley-Koch, S Bryn Austin, Esmina Avdibegoviç, Dragan Babić, Silviu-Alin Bacanu, Dewleen G Baker, Anthony BatzlerJean C Beckham, Sintia Belangero, Corina Benjet, AURORA Study

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avis › Tidsskriftartikel › Forskning › peer review

15 Citationer (Scopus)

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.

Originalsprog	Engelsk
Tidsskrift	Nature Genetics
Vol/bind	56
Nummer	5
Sider (fra-til)	792-808
Antal sider	17
ISSN	1061-4036
DOI	https://doi.org/10.1038/s41588-024-01707-9
Status	Udgivet - maj 2024

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Nievergelt, C. M., Maihofer, A. X., Atkinson, E. G., Chen, C.-Y., Choi, K. W., Coleman, J. R. I., Daskalakis, N. P., Duncan, L. E., Polimanti, R., Aaronson, C., Amstadter, A. B., Andreassen, O. A., Arbisi, P. A., Ashley-Koch, A. E., Austin, S. B., Avdibegoviç, E., Babić, D., Bacanu, S.-A., Baker, D. G., ... AURORA Study (2024). Genome-wide association analyses identify 95 risk loci and provide insights into the neurobiology of post-traumatic stress disorder. Nature Genetics, 56(5), 792-808. https://doi.org/10.1038/s41588-024-01707-9

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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.",

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year = "2024",

month = may,

doi = "10.1038/s41588-024-01707-9",

language = "English",

volume = "56",

pages = "792--808",

journal = "Nature Genetics",

issn = "1061-4036",

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Nievergelt, CM, Maihofer, AX, Atkinson, EG, Chen, C-Y, Choi, KW, Coleman, JRI, Daskalakis, NP, Duncan, LE, Polimanti, R, Aaronson, C, Amstadter, AB, Andreassen, OA, Arbisi, PA, Ashley-Koch, AE, Austin, SB, Avdibegoviç, E, Babić, D, Bacanu, S-A, Baker, DG, Batzler, A, Beckham, JC, Belangero, S, Benjet, C & AURORA Study 2024, 'Genome-wide association analyses identify 95 risk loci and provide insights into the neurobiology of post-traumatic stress disorder', Nature Genetics, bind 56, nr. 5, s. 792-808. https://doi.org/10.1038/s41588-024-01707-9

Genome-wide association analyses identify 95 risk loci and provide insights into the neurobiology of post-traumatic stress disorder. / Nievergelt, Caroline M; Maihofer, Adam X; Atkinson, Elizabeth G et al.
I: Nature Genetics, Bind 56, Nr. 5, 05.2024, s. 792-808.

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avis › Tidsskriftartikel › Forskning › peer review

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AU - Nievergelt, Caroline M

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AU - Choi, Karmel W

AU - Coleman, Jonathan R I

AU - Daskalakis, Nikolaos P

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AU - Aaronson, Cindy

AU - Amstadter, Ananda B

AU - Andreassen, Ole A

AU - Arbisi, Paul A

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AU - Benjet, Corina

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AU - Biernacka, Joanna M

AU - Bierut, Laura J

AU - Bisson, Jonathan I

AU - Boks, Marco P

AU - Bolger, Elizabeth A

AU - Brandolino, Amber

AU - Breen, Gerome

AU - Bressan, Rodrigo Affonseca

AU - Bryant, Richard A

AU - Bustamante, Angela C

AU - Bybjerg-Grauholm, Jonas

AU - Bækvad-Hansen, Marie

AU - Børglum, Anders D

AU - Børte, Sigrid

AU - Cahn, Leah

AU - Calabrese, Joseph R

AU - Caldas-de-Almeida, Jose Miguel

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N2 - 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.

AB - 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.

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KW - Genome-Wide Association Study

KW - Humans

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KW - Stress Disorders, Post-Traumatic/genetics

KW - White People/genetics

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JO - Nature Genetics

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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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