Browsing by Author "Javanbakht, Arash"

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    Alcohol Use and Alcohol Use Disorder Differ in their Genetic Relationships with PTSD: A Genomic Structural Equation Modelling Approach
    (Elsevier, 2022) Bountress, Kaitlin E.; Brick, Leslie A.; Sheerin, Christina; Grotzinger, Andrew; Bustamante, Daniel; Hawn, Sage E.; Gillespie, Nathan; Kirkpatrick, Robert M.; Kranzler, Henry; Morey, Rajendra; Edenberg, Howard J.; Maihofer, Adam X.; Disner, Seth; Ashley-Koch, Allison; Peterson, Roseann; Lori, Adriana; Stein, Dan J.; Kimbrel, Nathan; Nievergelt, Caroline; Andreassen, Ole A.; Luykx, Jurjen; Javanbakht, Arash; Youssef, Nagy A.; Psychiatric Genomics Consortium Posttraumatic Stress Disorder Working Group; Amstadter, Ananda B.; Biochemistry and Molecular Biology, School of Medicine
    Purpose: Posttraumatic Stress Disorder (PTSD) is associated with increased alcohol use and alcohol use disorder (AUD), which are all moderately heritable. Studies suggest the genetic association between PTSD and alcohol use differs from that of PTSD and AUD, but further analysis is needed. Basic procedures: We used genomic Structural Equation Modeling (genomicSEM) to analyze summary statistics from large-scale genome-wide association studies (GWAS) of European Ancestry participants to investigate the genetic relationships between PTSD (both diagnosis and re-experiencing symptom severity) and a range of alcohol use and AUD phenotypes. Main findings: When we differentiated genetic factors for alcohol use and AUD we observed improved model fit relative to models with all alcohol-related indicators loading onto a single factor. The genetic correlations (rG) of PTSD were quite discrepant for the alcohol use and AUD factors. This was true when modeled as a three-correlated-factor model (PTSD-AUD rG:.36, p < .001; PTSD-alcohol use rG: -0.17, p < .001) and as a Bifactor model, in which the common and unique portions of alcohol phenotypes were pulled out into an AUD-specific factor (rG with PTSD:.40, p < .001), AU-specific factor (rG with PTSD: -0.57, p < .001), and a common alcohol factor (rG with PTSD:.16, NS). Principal conclusions: These results indicate the genetic architecture of alcohol use and AUD are differentially associated with PTSD. When the portions of variance unique to alcohol use and AUD are extracted, their genetic associations with PTSD vary substantially, suggesting different genetic architectures of alcohol phenotypes in people with PTSD.
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    Genome-wide association analyses identify 95 risk loci and provide insights into the neurobiology of post-traumatic stress disorder
    (Springer Nature, 2024) 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; Amstadter, Ananda B.; Andersen, Soren B.; Andreassen, Ole A.; Arbisi, Paul A.; Ashley-Koch, Allison E.; Austin, S. Bryn; Avdibegoviç, Esmina; Babić, Dragan; Bacanu, Silviu-Alin; Baker, Dewleen G.; Batzler, Anthony; Beckham, Jean C.; Belangero, Sintia; Benjet, Corina; Bergner, Carisa; 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; Džubur Kulenović, Alma; 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.; Goçi, Aferdita; Grasser, Lana Ruvolo; Guindalini, Camila; Haas, Magali; Hagenaars, Saskia; Hauser, Michael A.; Heath, Andrew C.; Hemmings, Sian M. J.; Hesselbrock, Victor; 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.; Lupto, Michelle K.; Luykx, Jurjen J.; Makotkine, Iouri; Maples-Keller, Jessica L.; Marchese, Shelby; Marmar, Charles; Martin, Nicholas G.; Martínez-Levy, Gabriela A.; McAloney, Kerrie; McFarlane, Alexander; McLaughlin, Katie A.; McLean, Samuel A.; Medland, Sarah E.; Mehta, Divya; Meyers, Jacquelyn; Michopoulos, Vasiliki; Mikita, Elizabeth A.; Milani, Lili; Milberg, William; 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; 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; Runz, Heiko; Rutten, Bart P. F.; Saenz de Viteri, Stacey; Salum, Giovanni Abrahão; Sampson, Laura; Sanchez, Sixto E.; Santoro, Marcos; 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; 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; 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; 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; van Rooij, Sanne J. H.; van den Heuvel, Leigh L.; AURORA Study; Estonian Biobank Research Team; FinnGen Investigators; HUNT All-In Psychiatry; Stein, Murray B.; Ressler, Kerry J.; Koenen, Karestan C.; Biochemistry and Molecular Biology, School of Medicine
    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.