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.; Chen, Chia-Yen; Choi, Karmel W; Coleman, Jonathan R. I.; Daskalakis, Nikolaos P.; Duncan, Laramie E.; Polimanti, Renato; Aaronson, Cindy J; Amstadter, Ananda B.; Andersen, Soren B.; Andreassen, Ole A.; Arbisi, Paul A; Ashley-Koch, Allison E.; Austin, S Bryn; Avdibegovic, Esmina; Babic, Dragan; Bacanu, Silviu-Alin; Baker, Dewleen G; Batzler, Anthony; Beckham, Jean C.; Belangero, Sintia Nogueira; Benjet, Corina; Bergner, Carisa L; Bierer, Linda M.; Biernacka, Joanna M; Bierut, Laura J.; Bisson, Jonathan I; Boks, Marco P; Bolger, Elizabeth A.; Brandolino, Amber; Breen, Gerome; Bressan, Rodrigo Affonseca; Bryant, Richard A; Bustamante, Angela C.; Bybjerg-Grauholm, Jonas; Bækvad-Hansen, Marie; Børglum, Anders D.; Børte, Sigrid; Cahn, Leah; Calabrese, Joseph R.; Caldas-de-Almeida, Jose Miguel; Chatzinakos, Chris; Cheema, Sheraz; Clouston, Sean A. P.; Colodro-Conde, Lucía; Coombes, Brandon J; Cruz-Fuentes, Carlos S; Dale, Anders M.; Dalvie, Shareefa; Davis, Lea K; Deckert, Jürgen; Delahanty, Douglas L.; Dennis, Michelle F.; Desarnaud, Frank; DiPietro, Christopher P.; Disner, Seth G; Docherty, Anna R.; Domschke, Katharina; Dyb, Grete; Kulenovic, Alma Dzubur; Edenberg, Howard J; Evans, Alexandra; Fabbri, Chiara; Fani, Negar; Farrer, Lindsay A.; Feder, Adriana; Feeny, Norah C; Flory, Janine D.; Forbes, David; Franz, Carol E.; Galea, Sandro; Garrett, Melanie E.; Gelaye, Bizu; Gelernter, Joel; Geuze, Elbert; Gillespie, Charles F.; Goleva, Slavina B.; Gordon, Scott D.; Goci, Aferdita; Grasser, Lana Ruvolo; Guindalini, Camila; Haas, Magali; Hagenaars, Saskia; Hauser, Michael A.; Heath, Andrew C.; Hemmings, Sian M J; Hesselbrock, Victor M; Hickie, Ian B.; Hogan, Kelleigh; Hougaard, David Michael; Huang, Hailiang; Huckins, Laura M; Hveem, Kristian; Jakovljević, Miro; Javanbakht, Arash; Jenkins, Gregory D.; Johnson, Jessica; Jones, Ian; Jovanovic, Tanja; Karstoft, Karen-Inge; Kaufman, Milissa L.; Kennedy, James L.; Kessler, Ronald C; Khan, Alaptagin; Kimbrel, Nathan A.; King, Anthony P.; Koen, Nastassja; Kotov, Roman; Kranzler, Henry R; Krebs, Kristi; Kremen, William S.; Kuan, Pei-Fen; Lawford, Bruce R; Lebois, Lauren A M; Lehto, Kelli; Levey, Daniel F.; Lewis, Catrin; Liberzon, Israel; Linnstaedt, Sarah D.; Logue, Mark W; Lori, Adriana; Lu, Yi.; Luft, Benjamin J.; Lupton, Michelle K.; Luykx, Jurjen J; Makotkine, Iouri; Maples-Keller, Jessica L; Marchese, Shelby; Marmar, Charles Raymond; Martin, Nicholas G; Martínez-Levy, Gabriela A; McAloney, Kerrie; McFarlane, Alexander E.; McLaughlin, Katie A.; McLean, Samuel A.; Medland, Sarah E.; Mehta, Divya; Meyers, Jacquelyn; Michopoulos, Vasiliki; Mikita, Elizabeth A.; Milani, Lili; Milberg, William P.; Miller, Mark W; Morey, Rajendra A.; Morris, Charles Phillip; Mors, Ole; Mortensen, Preben Bo; Mufford, Mary S.; Nelson, Elliot C.; Nordentoft, Merete; Norman, Sonya B; Nugent, Nicole R.; O’Donnell, Meaghan L.; Orcutt, Holly K; Pan, Pedro M.; Panizzon, Matthew S.; Pathak, Gita A.; Peters, Edward S.; Peterson, Alan L.; Peverill, Matthew; Pietrzak, Robert H; Polusny, Melissa A; Porjesz, Bernice; Powers, Abigail; Qin, Xue-Jun; Ratanatharathorn, Andrew; Risbrough, Victoria B.; Roberts, Andrea L; Rothbaum, Alex O; Rothbaum, Barbara O; Roy-Byrne, Peter; Ruggiero, Kenneth J; Rung, Ariane Lisann; Runz, Heiko; Rutten, Bart P F; de Viteri, Stacey Saenz; Salum, Giovanni Abrahão; Sampson, Laura; Sánchez, Sixto E.; Santoro, Marcos L.; Seah, Carina; Seedat, Soraya; Seng, Julia S; Shabalin, Andrey; Sheerin, Christina M; Silove, Derrick; Smith, Alicia K.; Smoller, Jordan W.; Sponheim, Scott R.; Stein, Dan J.; Stensland, Synne Øien; Stevens, Jennifer S.; Sumner, Jennifer A.; Teicher, Martin H.; Thompson, Wesley K.; Tiwari, Arun K.; Trapido, Edward; Uddin, Monica; Ursano, Robert J; Valdimarsdóttir, Unnur; van Hooff, Miranda L; Vermetten, Eric; Vinkers, Christiaan H.; Voisey, Joanne; Wang, Yunpeng; Wang, Zhewu; Waszczuk, Monika; Weber, Heike; Wendt, Frank R; Werge, Thomas; Williams, Michelle A.; Williamson, Douglas E; Winsvold, Bendik S.; Winternitz, Sherry R.; Wolf, Christiane; Wolf, Erika J.; Xia, Yan; Xiong, Ying; Yehuda, Rachel; Young, Keith A; Young, Ross McD; Zai, Clement C; Zai, Gwyneth C.; Zervas, Mark; Zhao, Hongyu; Zoellner, Lori A; Zwart, John-Anker; deRoon-Cassini, Terri A; van Rooij, Sanne J H; van den Heuvel, Leigh L; Stein, Murray B; Ressler, Kerry J.; Koenen, Karestan C.

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

Author(s): 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 , Soren B. Andersen , 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 , Carisa Bergner , Linda M. Bierer , Joanna M. Biernacka , Laura J. Bierut , Jonathan I. Bisson , Marco P. Boks , Elizabeth A. Bolger , Amber Brandolino , Gerome Breen , Rodrigo Affonseca Bressan , Richard A. Bryant , Angela C. Bustamante , Jonas Bybjerg-Grauholm , Marie Bækvad-Hansen , Anders D. Børglum , Sigrid Børte , Leah Cahn , Joseph R. Calabrese , Jose Miguel Caldas-de-Almeida , Chris Chatzinakos , Sheraz Cheema , Sean A. P. Clouston , Lucía Colodro-Conde , Brandon J. Coombes , Carlos S. Cruz-Fuentes , Anders M. Dale , Shareefa Dalvie , Lea K. Davis , Jürgen Deckert , Douglas L. Delahanty , Michelle F. Dennis , Frank Desarnaud , Christopher P. DiPietro , Seth G. Disner , Anna R. Docherty , Katharina Domschke , Grete Dyb , Alma Džubur Kulenović , Howard J. Edenberg , Alexandra Evans , Chiara Fabbri , Negar Fani , Lindsay A. Farrer , Adriana Feder , Norah C. Feeny , Janine D. Flory , David Forbes , Carol E. Franz , Sandro Galea , Melanie E. Garrett , Bizu Gelaye , Joel Gelernter , Elbert Geuze , Charles F. Gillespie , Slavina B. Goleva , Scott D. Gordon , Aferdita Goçi , Lana Ruvolo Grasser , Camila Guindalini , Magali Haas , Saskia Hagenaars , Michael A. Hauser , Andrew C. Heath , Sian M. J. Hemmings , Victor Hesselbrock , Ian B. Hickie , Kelleigh Hogan , David Michael Hougaard , Hailiang Huang , Laura M. Huckins , Kristian Hveem , Miro Jakovljević , Arash Javanbakht , Gregory D. Jenkins , Jessica Johnson , Ian Jones , Tanja Jovanovic , Karen-Inge Karstoft , Milissa L. Kaufman , James L. Kennedy , Ronald C. Kessler , Alaptagin Khan , Nathan A. Kimbrel , Anthony P. King , Nastassja Koen , Roman Kotov , Henry R. Kranzler , Kristi Krebs , William S. Kremen , Pei-Fen Kuan , Bruce R. Lawford , Lauren A. M. Lebois , Kelli Lehto , Daniel F. Levey , Catrin Lewis , Israel Liberzon , Sarah D. Linnstaedt , Mark W. Logue , Adriana Lori , Yi Lu , Benjamin J. Luft , Michelle K. Lupton , Jurjen J. Luykx , Iouri Makotkine , Jessica L. Maples-Keller , Shelby Marchese , Charles Marmar , Nicholas G. Martin , Gabriela A. Martínez-Levy , Kerrie McAloney , Alexander McFarlane , Katie A. McLaughlin , Samuel A. McLean , Sarah E. Medland , Divya Mehta , Jacquelyn Meyers , Vasiliki Michopoulos , Elizabeth A. Mikita , Lili Milani , William Milberg , Mark W. Miller , Rajendra A. Morey , Charles Phillip Morris , Ole Mors , Preben Bo Mortensen , Mary S. Mufford , Elliot C. Nelson , Merete Nordentoft , Sonya B. Norman , Nicole R. Nugent , Meaghan O’Donnell , Holly K. Orcutt , Pedro M. Pan , Matthew S. Panizzon , Gita A. Pathak , Edward S. Peters , Alan L. Peterson , Matthew Peverill , Robert H. Pietrzak , Melissa A. Polusny , Bernice Porjesz , Abigail Powers , Xue-Jun Qin , Andrew Ratanatharathorn , Victoria B. Risbrough , Andrea L. Roberts , Alex O. Rothbaum , Barbara O. Rothbaum , Peter Roy-Byrne , Kenneth J. Ruggiero , Ariane Rung , Heiko Runz , Bart P. F. Rutten , Stacey Saenz de Viteri , Giovanni Abrahão Salum , Laura Sampson , Sixto E. Sanchez , Marcos Santoro , Carina Seah , Soraya Seedat , Julia S. Seng , Andrey Shabalin , Christina M. Sheerin , Derrick Silove , Alicia K. Smith , Jordan W. Smoller , Scott R. Sponheim , Dan J. Stein , Synne Stensland , Jennifer S. Stevens , Jennifer A. Sumner , Martin H. Teicher , Wesley K. Thompson , Arun K. Tiwari , Edward Trapido , Monica Uddin , Robert J. Ursano , Unnur Valdimarsdóttir , Miranda Van Hooff , Eric Vermetten , Christiaan H. Vinkers , Joanne Voisey , Yunpeng Wang , Zhewu Wang , Monika Waszczuk , Heike Weber , Frank R. Wendt , Thomas Werge , Michelle A. Williams , Douglas E. Williamson , Bendik S. Winsvold , Sherry Winternitz , Christiane Wolf , Erika J. Wolf , Yan Xia , Ying Xiong , Rachel Yehuda , Keith A. Young , Ross McD Young , Clement C. Zai , Gwyneth C. Zai , Mark Zervas , Hongyu Zhao , Lori A. Zoellner , John-Anker Zwart , Terri deRoon-Cassini , Sanne J. H. van Rooij , Leigh L. van den Heuvel , Murray B. Stein , Kerry J. Ressler , Karestan C. Koenen , AURORA Study, Estonian Biobank Research Team, FinnGen Investigators, HUNT All-In Psychiatry

Publication date (Electronic): April 18 2024

Journal: Nature Genetics

Publisher: Springer Science and Business Media LLC

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Lachlan Coin, Robert Garry, Oleksyk Taras (2018)

The 1000 Genomes Project set out to provide a comprehensive description of common human genetic variation by applying whole-genome sequencing to a diverse set of individuals from multiple populations. Here we report completion of the project, having reconstructed the genomes of 2,504 individuals from 26 populations using a combination of low-coverage whole-genome sequencing, deep exome sequencing, and dense microarray genotyping. We characterized a broad spectrum of genetic variation, in total over 88 million variants (84.7 million single nucleotide polymorphisms (SNPs), 3.6 million short insertions/deletions (indels), and 60,000 structural variants), all phased onto high-quality haplotypes. This resource includes >99% of SNP variants with a frequency of >1% for a variety of ancestries. We describe the distribution of genetic variation across the global sample, and discuss the implications for common disease studies.

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The Molecular Signatures Database (MSigDB) hallmark gene set collection.

Arthur Liberzon, Chet Birger, Helga Thorvaldsdóttir … (2015)

The Molecular Signatures Database (MSigDB) is one of the most widely used and comprehensive databases of gene sets for performing gene set enrichment analysis. Since its creation, MSigDB has grown beyond its roots in metabolic disease and cancer to include >10,000 gene sets. These better represent a wider range of biological processes and diseases, but the utility of the database is reduced by increased redundancy across, and heterogeneity within, gene sets. To address this challenge, here we use a combination of automated approaches and expert curation to develop a collection of "hallmark" gene sets as part of MSigDB. Each hallmark in this collection consists of a "refined" gene set, derived from multiple "founder" sets, that conveys a specific biological state or process and displays coherent expression. The hallmarks effectively summarize most of the relevant information of the original founder sets and, by reducing both variation and redundancy, provide more refined and concise inputs for gene set enrichment analysis.

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ANNOVAR: functional annotation of genetic variants from high-throughput sequencing data

Kai Wang, Mingyao Li, Hakon Hakonarson (2010)

High-throughput sequencing platforms are generating massive amounts of genetic variation data for diverse genomes, but it remains a challenge to pinpoint a small subset of functionally important variants. To fill these unmet needs, we developed the ANNOVAR tool to annotate single nucleotide variants (SNVs) and insertions/deletions, such as examining their functional consequence on genes, inferring cytogenetic bands, reporting functional importance scores, finding variants in conserved regions, or identifying variants reported in the 1000 Genomes Project and dbSNP. ANNOVAR can utilize annotation databases from the UCSC Genome Browser or any annotation data set conforming to Generic Feature Format version 3 (GFF3). We also illustrate a ‘variants reduction’ protocol on 4.7 million SNVs and indels from a human genome, including two causal mutations for Miller syndrome, a rare recessive disease. Through a stepwise procedure, we excluded variants that are unlikely to be causal, and identified 20 candidate genes including the causal gene. Using a desktop computer, ANNOVAR requires ∼4 min to perform gene-based annotation and ∼15 min to perform variants reduction on 4.7 million variants, making it practical to handle hundreds of human genomes in a day. ANNOVAR is freely available at http://www.openbioinformatics.org/annovar/ .