Genetic Epidemiology, Translational Neurogenomics, Psychiatric Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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37693460
TITLE
Discovery of 95 PTSD loci provides insight into genetic architecture and neurobiology of trauma and stress-related disorders.
ABSTRACT
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., ), developmental, axon guidance, and transcription factors (e.g., ), synaptic structure and function genes (e.g., ), and endocrine or immune regulators (e.g., ). 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.
DATE PUBLISHED
2023 Sep 02
HISTORY
PUBSTATUS PUBSTATUSDATE
medline 2023/09/11 06:43
pubmed 2023/09/11 06:42
entrez 2023/09/11 04:54
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Nievergelt CM Nievergelt Caroline M CM
Maihofer AX Maihofer Adam X AX
Atkinson EG Atkinson Elizabeth G EG
Chen CY Chen Chia-Yen CY
Choi KW Choi Karmel W KW
Coleman JR Coleman Jonathan Ri JR
Daskalakis NP Daskalakis Nikolaos P NP
Duncan LE Duncan Laramie E LE
Polimanti R Polimanti Renato R
Aaronson C Aaronson Cindy C
Amstadter AB Amstadter Ananda B AB
Andersen SB Andersen Soren B SB
Andreassen OA Andreassen Ole A OA
Arbisi PA Arbisi Paul A PA
Ashley-Koch AE Ashley-Koch Allison E AE
Austin SB Austin S Bryn SB
Avdibegoviç E Avdibegoviç Esmina E
Babic D Babic Dragan D
Bacanu SA Bacanu Silviu-Alin SA
Baker DG Baker Dewleen G DG
Batzler A Batzler Anthony A
Beckham JC Beckham Jean C JC
Belangero S Belangero Sintia S
Benjet C Benjet Corina C
Bergner C Bergner Carisa C
Bierer LM Bierer Linda M LM
Biernacka JM Biernacka Joanna M JM
Bierut LJ Bierut Laura J LJ
Bisson JI Bisson Jonathan I JI
Boks MP Boks Marco P MP
Bolger EA Bolger Elizabeth A EA
Brandolino A Brandolino Amber A
Breen G Breen Gerome G
Bressan RA Bressan Rodrigo Affonseca RA
Bryant RA Bryant Richard A RA
Bustamante AC Bustamante Angela C AC
Bybjerg-Grauholm J Bybjerg-Grauholm Jonas J
Bækvad-Hansen M Bækvad-Hansen Marie M
Børglum AD Børglum Anders D AD
Børte S Børte Sigrid S
Cahn L Cahn Leah L
Calabrese JR Calabrese Joseph R JR
Caldas-de-Almeida JM Caldas-de-Almeida Jose Miguel JM
Chatzinakos C Chatzinakos Chris C
Cheema S Cheema Sheraz S
Clouston SAP Clouston Sean A P SAP
Colodro-Conde L Colodro-Conde LucÍa L
Coombes BJ Coombes Brandon J BJ
Cruz-Fuentes CS Cruz-Fuentes Carlos S CS
Dale AM Dale Anders M AM
Dalvie S Dalvie Shareefa S
Davis LK Davis Lea K LK
Deckert J Deckert Jürgen J
Delahanty DL Delahanty Douglas L DL
Dennis MF Dennis Michelle F MF
deRoon-Cassini T deRoon-Cassini Terri T
Desarnaud F Desarnaud Frank F
DiPietro CP DiPietro Christopher P CP
Disner SG Disner Seth G SG
Docherty AR Docherty Anna R AR
Domschke K Domschke Katharina K
Dyb G Dyb Grete G
Kulenovic AD Kulenovic Alma Dzubur AD
Edenberg HJ Edenberg Howard J HJ
Evans A Evans Alexandra A
Fabbri C Fabbri Chiara C
Fani N Fani Negar N
Farrer LA Farrer Lindsay A LA
Feder A Feder Adriana A
Feeny NC Feeny Norah C NC
Flory JD Flory Janine D JD
Forbes D Forbes David D
Franz CE Franz Carol E CE
Galea S Galea Sandro S
Garrett ME Garrett Melanie E ME
Gelaye B Gelaye Bizu B
Gelernter J Gelernter Joel J
Geuze E Geuze Elbert E
Gillespie CF Gillespie Charles F CF
Goci A Goci Aferdita A
Goleva SB Goleva Slavina B SB
Gordon SD Gordon Scott D SD
Grasser LR Grasser Lana Ruvolo LR
Guindalini C Guindalini Camila C
Haas M Haas Magali M
Hagenaars S Hagenaars Saskia S
Hauser MA Hauser Michael A MA
Heath AC Heath Andrew C AC
Hemmings SM Hemmings Sian Mj SM
Hesselbrock V Hesselbrock Victor V
Hickie IB Hickie Ian B IB
Hogan K Hogan Kelleigh K
Hougaard DM Hougaard David Michael DM
Huang H Huang Hailiang H
Huckins LM Huckins Laura M LM
Hveem K Hveem Kristian K
Jakovljevic M Jakovljevic Miro M
Javanbakht A Javanbakht Arash A
Jenkins GD Jenkins Gregory D GD
Johnson J Johnson Jessica J
Jones I Jones Ian I
Jovanovic T Jovanovic Tanja T
Karstoft KI Karstoft Karen-Inge KI
Kaufman ML Kaufman Milissa L ML
Kennedy JL Kennedy James L JL
Kessler RC Kessler Ronald C RC
Khan A Khan Alaptagin A
Kimbrel NA Kimbrel Nathan A NA
King AP King Anthony P AP
Koen N Koen Nastassja N
Kotov R Kotov Roman R
Kranzler HR Kranzler Henry R HR
Krebs K Krebs Kristi K
Kremen WS Kremen William S WS
Kuan PF Kuan Pei-Fen PF
Lawford BR Lawford Bruce R BR
Lebois LAM Lebois Lauren A M LAM
Lehto K Lehto Kelli K
Levey DF Levey Daniel F DF
Lewis C Lewis Catrin C
Liberzon I Liberzon Israel I
Linnstaedt SD Linnstaedt Sarah D SD
Logue MW Logue Mark W MW
Lori A Lori Adriana A
Lu Y Lu Yi Y
Luft BJ Luft Benjamin J BJ
Lupton MK Lupton Michelle K MK
Luykx JJ Luykx Jurjen J JJ
Makotkine I Makotkine Iouri I
Maples-Keller JL Maples-Keller Jessica L JL
Marchese S Marchese Shelby S
Marmar C Marmar Charles C
Martin NG Martin Nicholas G NG
MartÍnez-Levy GA MartÍnez-Levy Gabriela A GA
McAloney K McAloney Kerrie K
McFarlane A McFarlane Alexander A
McLaughlin KA McLaughlin Katie A KA
McLean SA McLean Samuel A SA
Medland SE Medland Sarah E SE
Mehta D Mehta Divya D
Meyers J Meyers Jacquelyn J
Michopoulos V Michopoulos Vasiliki V
Mikita EA Mikita Elizabeth A EA
Milani L Milani Lili L
Milberg W Milberg William W
Miller MW Miller Mark W MW
Morey RA Morey Rajendra A RA
Morris CP Morris Charles Phillip CP
Mors O Mors Ole O
Mortensen PB Mortensen Preben Bo PB
Mufford MS Mufford Mary S MS
Nelson EC Nelson Elliot C EC
Nordentoft M Nordentoft Merete M
Norman SB Norman Sonya B SB
Nugent NR Nugent Nicole R NR
O'Donnell M O'Donnell Meaghan M
Orcutt HK Orcutt Holly K HK
Pan PM Pan Pedro M PM
Panizzon MS Panizzon Matthew S MS
Pathak GA Pathak Gita A GA
Peters ES Peters Edward S ES
Peterson AL Peterson Alan L AL
Peverill M Peverill Matthew M
Pietrzak RH Pietrzak Robert H RH
Polusny MA Polusny Melissa A MA
Porjesz B Porjesz Bernice B
Powers A Powers Abigail A
Qin XJ Qin Xue-Jun XJ
Ratanatharathorn A Ratanatharathorn Andrew A
Risbrough VB Risbrough Victoria B VB
Roberts AL Roberts Andrea L AL
Rothbaum BO Rothbaum Barbara O BO
Rothbaum AO Rothbaum Alex O AO
Roy-Byrne P Roy-Byrne Peter P
Ruggiero KJ Ruggiero Kenneth J KJ
Rung A Rung Ariane A
Runz H Runz Heiko H
Rutten BPF Rutten Bart P F BPF
de Viteri SS de Viteri Stacey Saenz SS
Salum GA Salum Giovanni Abrahão GA
Sampson L Sampson Laura L
Sanchez SE Sanchez Sixto E SE
Santoro M Santoro Marcos M
Seah C Seah Carina C
Seedat S Seedat Soraya S
Seng JS Seng Julia S JS
Shabalin A Shabalin Andrey A
Sheerin CM Sheerin Christina M CM
Silove D Silove Derrick D
Smith AK Smith Alicia K AK
Smoller JW Smoller Jordan W JW
Sponheim SR Sponheim Scott R SR
Stein DJ Stein Dan J DJ
Stensland S Stensland Synne S
Stevens JS Stevens Jennifer S JS
Sumner JA Sumner Jennifer A JA
Teicher MH Teicher Martin H MH
Thompson WK Thompson Wesley K WK
Tiwari AK Tiwari Arun K AK
Trapido E Trapido Edward E
Uddin M Uddin Monica M
Ursano RJ Ursano Robert J RJ
Valdimarsdóttir U Valdimarsdóttir Unnur U
van den Heuvel LL van den Heuvel Leigh Luella LL
Van Hooff M Van Hooff Miranda M
van Rooij SJ van Rooij Sanne Jh SJ
Vermetten E Vermetten Eric E
Vinkers CH Vinkers Christiaan H CH
Voisey J Voisey Joanne J
Wang Z Wang Zhewu Z
Wang Y Wang Yunpeng Y
Waszczuk M Waszczuk Monika M
Weber H Weber Heike H
Wendt FR Wendt Frank R FR
Werge T Werge Thomas T
Williams MA Williams Michelle A MA
Williamson DE Williamson Douglas E DE
Winsvold BS Winsvold Bendik S BS
Winternitz S Winternitz Sherry S
Wolf EJ Wolf Erika J EJ
Wolf C Wolf Christiane C
Xia Y Xia Yan Y
Xiong Y Xiong Ying Y
Yehuda R Yehuda Rachel R
Young RM Young Ross McD RM
Young KA Young Keith A KA
Zai CC Zai Clement C CC
Zai GC Zai Gwyneth C GC
Zervas M Zervas Mark M
Zhao H Zhao Hongyu H
Zoellner LA Zoellner Lori A LA
Zwart JA Zwart John-Anker JA
Stein MB Stein Murray B MB
Ressler KJ Ressler Kerry J KJ
Koenen KC Koenen Karestan C KC
INVESTIGATORS
JOURNAL
VOLUME:
ISSUE:
TITLE: medRxiv : the preprint server for health sciences
ISOABBREVIATION: medRxiv
YEAR: 2023
MONTH: Sep
DAY: 02
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN:
ISSNTYPE:
MEDLINE JOURNAL
MEDLINETA: medRxiv
COUNTRY: United States
ISSNLINKING:
NLMUNIQUEID: 101767986
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Preprint
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