Abstract
Background: The causal effects of gut microbiome and the development of posttraumatic stress disorder (PTSD) are still unknown. This study aimed to clarify their potential causal association using mendelian randomization (MR). Methods: The summary-level statistics for gut microbiome were retrieved from a genome-wide association study (GWAS) of the MiBioGen consortium. As to PTSD, the Freeze 2 datasets were originated from the Psychiatric Genomics Consortium Posttraumatic Stress Disorder Working Group (PGC-PTSD), and the replicated datasets were obtained from FinnGen consortium. Single nucleotide polymorphisms meeting MR assumptions were selected as instrumental variables. The inverse variance weighting (IVW) method was employed as the main approach, supplemented by sensitivity analyses to evaluate potential pleiotropy and heterogeneity and ensure the robustness of the MR results. We also performed reverse MR analyses to explore PTSD’s causal effects on the relative abundances of specific features of the gut microbiome. Results: In Freeze 2 datasets from PGC-PTSD, eight bacterial traits revealed a potential causal association between gut microbiome and PTSD (IVW, all P < 0.05). In addition, Genus.Dorea and genus.Sellimonas were replicated in FinnGen datasets, in which eight bacterial traits revealed a potential causal association between gut microbiome and the occurrence of PTSD. The heterogeneity and pleiotropy analyses further supported the robustness of the IVW findings, providing additional evidence for their reliability. Conclusion: Our study provides the potential causal impact of gut microbiomes on the development of PTSD, shedding new light on the understanding of the dysfunctional gut-brain axis in this disorder. Our findings present novel evidence and call for investigations to confirm the association between their links, as well as to illuminate the underlying mechanisms.
Original language | English |
---|---|
Article number | 67 |
Journal | Translational Psychiatry |
Volume | 14 |
Issue number | 1 |
DOIs | |
Publication status | Published - 1 Dec 2024 |
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In: Translational Psychiatry, Vol. 14, No. 1, 67, 01.12.2024.
Research output: Contribution to journal › Article › Academic › peer-review
TY - JOUR
T1 - Potential causal association between gut microbiome and posttraumatic stress disorder
AU - The Psychiatric Genomics Consortium Posttraumatic Stress Disorder Working Group
AU - He, Qiang
AU - Wang, Wenjing
AU - Xu, Dingkang
AU - Xiong, Yang
AU - Tao, Chuanyuan
AU - You, Chao
AU - Ma, Lu
AU - Ma, Junpeng
AU - Nievergelt, Caroline M.
AU - Maihofer, Adam X.
AU - Klengel, Torsten
AU - Atkinson, Elizabeth G.
AU - Chen, Chia Yen
AU - Choi, Karmel W.
AU - Coleman, Jonathan R.I.
AU - Dalvie, Shareefa
AU - Duncan, Laramie E.
AU - Logue, Mark W.
AU - Provost, Allison C.
AU - Ratanatharathorn, Andrew
AU - Stein, Murray B.
AU - Torres, Katy
AU - Aiello, Allison E.
AU - Almli, Lynn M.
AU - Amstadter, Ananda B.
AU - Andersen, Søren B.
AU - Andreassen, Ole A.
AU - Arbisi, Paul A.
AU - Ashley-Koch, Allison E.
AU - Austin, S. Bryn
AU - Avdibegovic, Esmina
AU - Babić, Dragan
AU - Bækvad-Hansen, Marie
AU - Baker, Dewleen G.
AU - Beckham, Jean C.
AU - Bierut, Laura J.
AU - Bisson, Jonathan I.
AU - Boks, Marco P.
AU - Bolger, Elizabeth A.
AU - Børglum, Anders D.
AU - Bradley, Bekh
AU - Brashear, Megan
AU - Breen, Gerome
AU - Bryant, Richard A.
AU - Bustamante, Angela C.
AU - Bybjerg-Grauholm, Jonas
AU - Calabrese, Joseph R.
AU - Caldas-de-Almeida, José M.
AU - Luykx, Jurjen J.
AU - Vinkers, Christiaan H.
AU - Dale, Anders M.
AU - Daly, Mark J.
AU - Daskalakis, Nikolaos P.
AU - Deckert, J. rgen
AU - Delahanty, Douglas L.
AU - Dennis, Michelle F.
AU - Disner, Seth G.
AU - Domschke, Katharina
AU - Dzubur-Kulenovic, Alma
AU - Erbes, Christopher R.
AU - Evans, Alexandra
AU - Farrer, Lindsay A.
AU - Feeny, Norah C.
AU - Flory, Janine D.
AU - Forbes, David
AU - Franz, Carol E.
AU - Galea, Sandro
AU - Garrett, Melanie E.
AU - Gelaye, Bizu
AU - Gelernter, Joel
AU - Geuze, Elbert
AU - Gillespie, Charles
AU - Uka, Aferdita Goci
AU - Gordon, Scott D.
AU - Guffanti, Guia
AU - Hammamieh, Rasha
AU - Harnal, Supriya
AU - Hauser, Michael A.
AU - Heath, Andrew C.
AU - Hemmings, Sian M. J.
AU - Hougaard, David Michael
AU - Jakovljevic, Miro
AU - Jett, Marti
AU - Johnson, Eric Otto
AU - Jones, Ian
AU - Jovanovic, Tanja
AU - Qin, Xue-Jun
AU - Junglen, Angela G.
AU - Karstoft, Karen-Inge
AU - Kaufman, Milissa L.
AU - Kessler, Ronald C.
AU - Khan, Alaptagin
AU - Kimbrel, Nathan A.
AU - King, Anthony P.
AU - Koen, Nastassja
AU - Kranzler, Henry R.
AU - Kremen, William S.
AU - Lawford, Bruce R.
AU - Lebois, Lauren A. M.
AU - Lewis, Catrin E.
AU - Linnstaedt, Sarah D.
AU - Lori, Adriana
AU - Lugonja, Bozo
AU - Lyons, Michael J.
AU - Maples-Keller, Jessica
AU - Marmar, Charles
AU - Martin, Alicia R.
AU - Martin, Nicholas G.
AU - Maurer, Douglas
AU - Mavissakalian, Matig R.
AU - McFarlane, Alexander
AU - McGlinchey, Regina E.
AU - McLaughlin, Katie A.
AU - McLean, Samuel A.
AU - McLeay, Sarah
AU - Mehta, Divya
AU - Milberg, William P.
AU - Miller, Mark W.
AU - Morey, Rajendra A.
AU - Morris, Charles Phillip
AU - Mors, Ole
AU - Mortensen, Preben B.
AU - Neale, Benjamin M.
AU - Nelson, Elliot C.
AU - Nordentoft, Merete
AU - Norman, Sonya B.
AU - O’Donnell, Meaghan
AU - Orcutt, Holly K.
AU - Panizzon, Matthew S.
AU - Peters, Edward S.
AU - Peterson, Alan L.
AU - Peverill, Matthew
AU - Pietrzak, Robert H.
AU - Polusny, Melissa A.
AU - Rice, John P.
AU - Ripke, Stephan
AU - Risbrough, Victoria B.
AU - Roberts, Andrea L.
AU - Rothbaum, Alex O.
AU - Rothbaum, Barbara O.
AU - Roy-Byrne, Peter
AU - Ruggiero, Ken
AU - Rung, Ariane
AU - Rutten, Bart P. F.
AU - Saccone, Nancy L.
AU - Sanchez, Sixto E.
AU - Schijven, Dick
AU - Seedat, Soraya
AU - Seligowski, Antonia V.
AU - Seng, Julia S.
AU - Sheerin, Christina M.
AU - Silove, Derrick
AU - Smith, Alicia K.
AU - Smoller, Jordan W.
AU - Solovieff, Nadia
AU - Sponheim, Scott R.
AU - Stein, Dan J.
AU - Sumner, Jennifer A.
AU - Teicher, Martin H.
AU - Thompson, Wesley K.
AU - Trapido, Edward
AU - Uddin, Monica
AU - Ursano, Robert J.
AU - van den Heuvel, Leigh Luella
AU - van Hooff, Miranda
AU - Vermetten, Eric
AU - Voisey, Joanne
AU - Wang, Yunpeng
AU - Wang, Zhewu
AU - Werge, Thomas
AU - Williams, Michelle A.
AU - Williamson, Douglas E.
AU - Winternitz, Sherry
AU - Wolf, Christiane
AU - Wolf, Erika J.
AU - Wolff, Jonathan D.
AU - Yehuda, Rachel
AU - Young, Keith A.
AU - Young, Ross McD
AU - Zhao, Hongyu
AU - Zoellner, Lori A.
AU - Liberzon, Israel
AU - Ressler, Kerry J.
AU - Haas, Magali
AU - Koenen, Karestan C.
N1 - Publisher Copyright: © 2024, The Author(s).
PY - 2024/12/1
Y1 - 2024/12/1
N2 - Background: The causal effects of gut microbiome and the development of posttraumatic stress disorder (PTSD) are still unknown. This study aimed to clarify their potential causal association using mendelian randomization (MR). Methods: The summary-level statistics for gut microbiome were retrieved from a genome-wide association study (GWAS) of the MiBioGen consortium. As to PTSD, the Freeze 2 datasets were originated from the Psychiatric Genomics Consortium Posttraumatic Stress Disorder Working Group (PGC-PTSD), and the replicated datasets were obtained from FinnGen consortium. Single nucleotide polymorphisms meeting MR assumptions were selected as instrumental variables. The inverse variance weighting (IVW) method was employed as the main approach, supplemented by sensitivity analyses to evaluate potential pleiotropy and heterogeneity and ensure the robustness of the MR results. We also performed reverse MR analyses to explore PTSD’s causal effects on the relative abundances of specific features of the gut microbiome. Results: In Freeze 2 datasets from PGC-PTSD, eight bacterial traits revealed a potential causal association between gut microbiome and PTSD (IVW, all P < 0.05). In addition, Genus.Dorea and genus.Sellimonas were replicated in FinnGen datasets, in which eight bacterial traits revealed a potential causal association between gut microbiome and the occurrence of PTSD. The heterogeneity and pleiotropy analyses further supported the robustness of the IVW findings, providing additional evidence for their reliability. Conclusion: Our study provides the potential causal impact of gut microbiomes on the development of PTSD, shedding new light on the understanding of the dysfunctional gut-brain axis in this disorder. Our findings present novel evidence and call for investigations to confirm the association between their links, as well as to illuminate the underlying mechanisms.
AB - Background: The causal effects of gut microbiome and the development of posttraumatic stress disorder (PTSD) are still unknown. This study aimed to clarify their potential causal association using mendelian randomization (MR). Methods: The summary-level statistics for gut microbiome were retrieved from a genome-wide association study (GWAS) of the MiBioGen consortium. As to PTSD, the Freeze 2 datasets were originated from the Psychiatric Genomics Consortium Posttraumatic Stress Disorder Working Group (PGC-PTSD), and the replicated datasets were obtained from FinnGen consortium. Single nucleotide polymorphisms meeting MR assumptions were selected as instrumental variables. The inverse variance weighting (IVW) method was employed as the main approach, supplemented by sensitivity analyses to evaluate potential pleiotropy and heterogeneity and ensure the robustness of the MR results. We also performed reverse MR analyses to explore PTSD’s causal effects on the relative abundances of specific features of the gut microbiome. Results: In Freeze 2 datasets from PGC-PTSD, eight bacterial traits revealed a potential causal association between gut microbiome and PTSD (IVW, all P < 0.05). In addition, Genus.Dorea and genus.Sellimonas were replicated in FinnGen datasets, in which eight bacterial traits revealed a potential causal association between gut microbiome and the occurrence of PTSD. The heterogeneity and pleiotropy analyses further supported the robustness of the IVW findings, providing additional evidence for their reliability. Conclusion: Our study provides the potential causal impact of gut microbiomes on the development of PTSD, shedding new light on the understanding of the dysfunctional gut-brain axis in this disorder. Our findings present novel evidence and call for investigations to confirm the association between their links, as well as to illuminate the underlying mechanisms.
UR - http://www.scopus.com/inward/record.url?scp=85184147737&partnerID=8YFLogxK
U2 - 10.1038/s41398-024-02765-7
DO - 10.1038/s41398-024-02765-7
M3 - Article
C2 - 38296956
SN - 2158-3188
VL - 14
JO - Translational Psychiatry
JF - Translational Psychiatry
IS - 1
M1 - 67
ER -