TY - UNPB
T1 - Discovery of 95 PTSD loci provides insight into genetic architecture and neurobiology of trauma and stress-related disorders
AU - Nievergelt, Caroline M
AU - Maihofer, Adam X
AU - Atkinson, Elizabeth G
AU - Chen, Chia-Yen
AU - Choi, Karmel W
AU - Coleman, Jonathan Ri
AU - Daskalakis, Nikolaos P
AU - Duncan, Laramie E
AU - Polimanti, Renato
AU - Aaronson, Cindy
AU - Amstadter, Ananda B
AU - Andersen, Soren B
AU - Andreassen, Ole A
AU - Arbisi, Paul A
AU - Ashley-Koch, Allison E
AU - Austin, S Bryn
AU - Avdibegoviç, Esmina
AU - Babic, Dragan
AU - Bacanu, Silviu-Alin
AU - Baker, Dewleen G
AU - Batzler, Anthony
AU - Beckham, Jean C
AU - Belangero, Sintia
AU - Benjet, Corina
AU - Bergner, Carisa
AU - Bierer, Linda M
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
AU - Chatzinakos, Chris
AU - Cheema, Sheraz
AU - Clouston, Sean A P
AU - Colodro-Conde, LucÍa
AU - Nordentoft, Merete
AU - Thompson, Wesley K
AU - Werge, Thomas
PY - 2023/9/2
Y1 - 2023/9/2
N2 - Posttraumatic 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 novel). Convergent multi-omic approaches identified 43 potential causal genes, broadly classified as neurotransmitter and ion channel synaptic modulators (e.g., GRIA1, GRM8, CACNA1E ), developmental, axon guidance, and transcription factors (e.g., FOXP2, EFNA5, DCC ), synaptic structure and function genes (e.g., PCLO, NCAM1, PDE4B ), and endocrine or immune regulators (e.g., ESR1, TRAF3, 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 - Posttraumatic 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 novel). Convergent multi-omic approaches identified 43 potential causal genes, broadly classified as neurotransmitter and ion channel synaptic modulators (e.g., GRIA1, GRM8, CACNA1E ), developmental, axon guidance, and transcription factors (e.g., FOXP2, EFNA5, DCC ), synaptic structure and function genes (e.g., PCLO, NCAM1, PDE4B ), and endocrine or immune regulators (e.g., ESR1, TRAF3, 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.
U2 - 10.1101/2023.08.31.23294915
DO - 10.1101/2023.08.31.23294915
M3 - Preprint
C2 - 37693460
T3 - medRxiv : the preprint server for health sciences
BT - Discovery of 95 PTSD loci provides insight into genetic architecture and neurobiology of trauma and stress-related disorders
ER -