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1. Genome-wide association analyses identify 95 risk loci and provide insights into the neurobiology of post-traumatic stress disorder

Author

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, Kulenović, Alma Džubur, 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., Lupton, 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., de Viteri, Stacey Saenz, 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., Stein, Murray B., Ressler, Kerry J., and Koenen, Karestan C.

Published
2024
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3. Rare copy number variation in posttraumatic stress disorder

Author

Maihofer, Adam X, Engchuan, Worrawat, Huguet, Guillaume, Klein, Marieke, MacDonald, Jeffrey R, Shanta, Omar, Thiruvahindrapuram, Bhooma, Jean-louis, Martineau, Saci, Zohra, Jacquemont, Sebastien, Scherer, Stephen W, Ketema, Elizabeth, Aiello, Allison E, Amstadter, Ananda B, Avdibegović, Esmina, Babic, Dragan, Baker, Dewleen G, Bisson, Jonathan I, Boks, Marco P, Bolger, Elizabeth A, Bryant, Richard A, Bustamante, Angela C, Caldas-de-Almeida, Jose Miguel, Cardoso, Graça, Deckert, Jurgen, Delahanty, Douglas L, Domschke, Katharina, Dunlop, Boadie W, Dzubur-Kulenovic, Alma, Evans, Alexandra, Feeny, Norah C, Franz, Carol E, Gautam, Aarti, Geuze, Elbert, Goci, Aferdita, Hammamieh, Rasha, Jakovljevic, Miro, Jett, Marti, Jones, Ian, Kaufman, Milissa L, Kessler, Ronald C, King, Anthony P, Kremen, William S, Lawford, Bruce R, Lebois, Lauren AM, Lewis, Catrin, Liberzon, Israel, Linnstaedt, Sarah D, Lugonja, Bozo, Luykx, Jurjen J, Lyons, Michael J, Mavissakalian, Matig R, McLaughlin, Katie A, McLean, Samuel A, Mehta, Divya, Mellor, Rebecca, Morris, Charles Phillip, Muhie, Seid, Orcutt, Holly K, Peverill, Matthew, Ratanatharathorn, Andrew, Risbrough, Victoria B, Rizzo, Albert, Roberts, Andrea L, Rothbaum, Alex O, Rothbaum, Barbara O, Roy-Byrne, Peter, Ruggiero, Kenneth J, Rutten, Bart PF, Schijven, Dick, Seng, Julia S, Sheerin, Christina M, Sorenson, Michael A, Teicher, Martin H, Uddin, Monica, Ursano, Robert J, Vinkers, Christiaan H, Voisey, Joanne, Weber, Heike, Winternitz, Sherry, Xavier, Miguel, Yang, Ruoting, McD Young, Ross, Zoellner, Lori A, Salem, Rany M, Shaffer, Richard A, Wu, Tianying, Ressler, Kerry J, Stein, Murray B, Koenen, Karestan C, Sebat, Jonathan, and Nievergelt, Caroline M

Subjects
Post-Traumatic Stress Disorder (PTSD), Mental Health, Human Genome, Genetics, Neurosciences, Brain Disorders, Mental health, Humans, DNA Copy Number Variations, Stress Disorders, Post-Traumatic, Genome, Brain, Genome-Wide Association Study, Polymorphism, Single Nucleotide, Genetic Predisposition to Disease, Psychiatric Genomics Consortium PTSD Working Group, Psychiatric Genomics Consortium CNV Working Group, Biological Sciences, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry
Abstract

Posttraumatic stress disorder (PTSD) is a heritable (h2 = 24-71%) psychiatric illness. Copy number variation (CNV) is a form of rare genetic variation that has been implicated in the etiology of psychiatric disorders, but no large-scale investigation of CNV in PTSD has been performed. We present an association study of CNV burden and PTSD symptoms in a sample of 114,383 participants (13,036 cases and 101,347 controls) of European ancestry. CNVs were called using two calling algorithms and intersected to a consensus set. Quality control was performed to remove strong outlier samples. CNVs were examined for association with PTSD within each cohort using linear or logistic regression analysis adjusted for population structure and CNV quality metrics, then inverse variance weighted meta-analyzed across cohorts. We examined the genome-wide total span of CNVs, enrichment of CNVs within specified gene-sets, and CNVs overlapping individual genes and implicated neurodevelopmental regions. The total distance covered by deletions crossing over known neurodevelopmental CNV regions was significant (beta = 0.029, SE = 0.005, P = 6.3 × 10-8). The genome-wide neurodevelopmental CNV burden identified explains 0.034% of the variation in PTSD symptoms. The 15q11.2 BP1-BP2 microdeletion region was significantly associated with PTSD (beta = 0.0206, SE = 0.0056, P = 0.0002). No individual significant genes interrupted by CNV were identified. 22 gene pathways related to the function of the nervous system and brain were significant in pathway analysis (FDR q

Published
2022

4. Enhancing Discovery of Genetic Variants for Posttraumatic Stress Disorder Through Integration of Quantitative Phenotypes and Trauma Exposure Information

Author

Maihofer, Adam X, Choi, Karmel W, Coleman, Jonathan RI, Daskalakis, Nikolaos P, Denckla, Christy A, Ketema, Elizabeth, Morey, Rajendra A, Polimanti, Renato, Ratanatharathorn, Andrew, Torres, Katy, Wingo, Aliza P, Zai, Clement C, Aiello, Allison E, Almli, Lynn M, Amstadter, Ananda B, Andersen, Soren B, Andreassen, Ole A, Arbisi, Paul A, Ashley-Koch, Allison E, Austin, S Bryn, Avdibegović, Esmina, Borglum, Anders D, Babić, Dragan, Bækvad-Hansen, Marie, Baker, Dewleen G, Beckham, Jean C, Bierut, Laura J, Bisson, Jonathan I, Boks, Marco P, Bolger, Elizabeth A, Bradley, Bekh, Brashear, Meghan, Breen, Gerome, Bryant, Richard A, Bustamante, Angela C, Bybjerg-Grauholm, Jonas, Calabrese, Joseph R, Caldas-de-Almeida, José M, Chen, Chia-Yen, Dale, Anders M, Dalvie, Shareefa, Deckert, Jürgen, Delahanty, Douglas L, Dennis, Michelle F, Disner, Seth G, Domschke, Katharina, Duncan, Laramie E, Džubur Kulenović, Alma, Erbes, Christopher R, Evans, Alexandra, Farrer, Lindsay A, Feeny, Norah C, Flory, Janine D, Forbes, David, Franz, Carol E, Galea, Sandro, Garrett, Melanie E, Gautam, Aarti, Gelaye, Bizu, Gelernter, Joel, Geuze, Elbert, Gillespie, Charles F, Goçi, Aferdita, Gordon, Scott D, Guffanti, Guia, Hammamieh, Rasha, Hauser, Michael A, Heath, Andrew C, Hemmings, Sian MJ, Hougaard, David Michael, Jakovljević, Miro, Jett, Marti, Johnson, Eric Otto, Jones, Ian, Jovanovic, Tanja, Qin, Xue-Jun, Karstoft, Karen-Inge, Kaufman, Milissa L, Kessler, Ronald C, Khan, Alaptagin, Kimbrel, Nathan A, King, Anthony P, Koen, Nastassja, Kranzler, Henry R, Kremen, William S, Lawford, Bruce R, Lebois, Lauren AM, Lewis, Catrin, Liberzon, Israel, Linnstaedt, Sarah D, Logue, Mark W, Lori, Adriana, Lugonja, Božo, Luykx, Jurjen J, Lyons, Michael J, Maples-Keller, Jessica L, Marmar, Charles, Martin, Nicholas G, Maurer, Douglas, and Mavissakalian, Matig R

Subjects
Biological Sciences, Genetics, Anxiety Disorders, Mental Health, Brain Disorders, Post-Traumatic Stress Disorder (PTSD), Prevention, Human Genome, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Phenotype, Polymorphism, Single Nucleotide, Stress Disorders, Post-Traumatic, GWAS, Heritability, PTSD, PheWAS, Trauma, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry, Biological sciences, Biomedical and clinical sciences, Psychology
Abstract

BackgroundPosttraumatic stress disorder (PTSD) is heritable and a potential consequence of exposure to traumatic stress. Evidence suggests that a quantitative approach to PTSD phenotype measurement and incorporation of lifetime trauma exposure (LTE) information could enhance the discovery power of PTSD genome-wide association studies (GWASs).MethodsA GWAS on PTSD symptoms was performed in 51 cohorts followed by a fixed-effects meta-analysis (N = 182,199 European ancestry participants). A GWAS of LTE burden was performed in the UK Biobank cohort (N = 132,988). Genetic correlations were evaluated with linkage disequilibrium score regression. Multivariate analysis was performed using Multi-Trait Analysis of GWAS. Functional mapping and annotation of leading loci was performed with FUMA. Replication was evaluated using the Million Veteran Program GWAS of PTSD total symptoms.ResultsGWASs of PTSD symptoms and LTE burden identified 5 and 6 independent genome-wide significant loci, respectively. There was a 72% genetic correlation between PTSD and LTE. PTSD and LTE showed largely similar patterns of genetic correlation with other traits, albeit with some distinctions. Adjusting PTSD for LTE reduced PTSD heritability by 31%. Multivariate analysis of PTSD and LTE increased the effective sample size of the PTSD GWAS by 20% and identified 4 additional loci. Four of these 9 PTSD loci were independently replicated in the Million Veteran Program.ConclusionsThrough using a quantitative trait measure of PTSD, we identified novel risk loci not previously identified using prior case-control analyses. PTSD and LTE have a high genetic overlap that can be leveraged to increase discovery power through multivariate methods.

Published
2022

5. International meta-analysis of PTSD genome-wide association studies identifies sex- and ancestry-specific genetic risk loci.

Author

Nievergelt, Caroline M, Maihofer, Adam X, Klengel, Torsten, Atkinson, Elizabeth G, Chen, Chia-Yen, Choi, Karmel W, Coleman, Jonathan RI, Dalvie, Shareefa, Duncan, Laramie E, Gelernter, Joel, Levey, Daniel F, Logue, Mark W, Polimanti, Renato, Provost, Allison C, Ratanatharathorn, Andrew, Stein, Murray B, Torres, Katy, Aiello, Allison E, Almli, Lynn M, Amstadter, Ananda B, Andersen, Søren B, Andreassen, Ole A, Arbisi, Paul A, Ashley-Koch, Allison E, Austin, S Bryn, Avdibegovic, Esmina, Babić, Dragan, Bækvad-Hansen, Marie, Baker, Dewleen G, Beckham, Jean C, Bierut, Laura J, Bisson, Jonathan I, Boks, Marco P, Bolger, Elizabeth A, Børglum, Anders D, Bradley, Bekh, Brashear, Megan, Breen, Gerome, Bryant, Richard A, Bustamante, Angela C, Bybjerg-Grauholm, Jonas, Calabrese, Joseph R, Caldas-de-Almeida, José M, Dale, Anders M, Daly, Mark J, Daskalakis, Nikolaos P, Deckert, Jürgen, Delahanty, Douglas L, Dennis, Michelle F, Disner, Seth G, Domschke, Katharina, Dzubur-Kulenovic, Alma, Erbes, Christopher R, Evans, Alexandra, Farrer, Lindsay A, Feeny, Norah C, Flory, Janine D, Forbes, David, Franz, Carol E, Galea, Sandro, Garrett, Melanie E, Gelaye, Bizu, Geuze, Elbert, Gillespie, Charles, Uka, Aferdita Goci, Gordon, Scott D, Guffanti, Guia, Hammamieh, Rasha, Harnal, Supriya, Hauser, Michael A, Heath, Andrew C, Hemmings, Sian MJ, Hougaard, David Michael, Jakovljevic, Miro, Jett, Marti, Johnson, Eric Otto, Jones, Ian, Jovanovic, Tanja, Qin, Xue-Jun, Junglen, Angela G, Karstoft, Karen-Inge, Kaufman, Milissa L, Kessler, Ronald C, Khan, Alaptagin, Kimbrel, Nathan A, King, Anthony P, Koen, Nastassja, Kranzler, Henry R, Kremen, William S, Lawford, Bruce R, Lebois, Lauren AM, Lewis, Catrin E, Linnstaedt, Sarah D, Lori, Adriana, Lugonja, Bozo, Luykx, Jurjen J, Lyons, Michael J, Maples-Keller, Jessica, Marmar, Charles, and Martin, Alicia R

Subjects
Humans, Genetic Predisposition to Disease, Ubiquitin-Protein Ligases, Stress Disorders, Post-Traumatic, Sex Factors, African Continental Ancestry Group, European Continental Ancestry Group, Veterans, Female, Male, Genome-Wide Association Study, Genetic Loci, Datasets as Topic, Human Genome, Mental Health, Biotechnology, Clinical Research, Post-Traumatic Stress Disorder (PTSD), Anxiety Disorders, Prevention, Genetics
Abstract

The risk of posttraumatic stress disorder (PTSD) following trauma is heritable, but robust common variants have yet to be identified. In a multi-ethnic cohort including over 30,000 PTSD cases and 170,000 controls we conduct a genome-wide association study of PTSD. We demonstrate SNP-based heritability estimates of 5-20%, varying by sex. Three genome-wide significant loci are identified, 2 in European and 1 in African-ancestry analyses. Analyses stratified by sex implicate 3 additional loci in men. Along with other novel genes and non-coding RNAs, a Parkinson's disease gene involved in dopamine regulation, PARK2, is associated with PTSD. Finally, we demonstrate that polygenic risk for PTSD is significantly predictive of re-experiencing symptoms in the Million Veteran Program dataset, although specific loci did not replicate. These results demonstrate the role of genetic variation in the biology of risk for PTSD and highlight the necessity of conducting sex-stratified analyses and expanding GWAS beyond European ancestry populations.

Published
2019

6. The Relationship of Attention-Deficit/Hyperactivity Disorder With Posttraumatic Stress Disorder: A Two-Sample Mendelian Randomization and Population-Based Sibling Comparison Study

Author

Maihofer, Adam X., Choi, Karmel W., Coleman, Jonathan R.I., Daskalakis, Nikolaos P., Denckla, Christy A., Ketema, Elizabeth, Morey, Rajendra A., Polimanti, Renato, Ratanatharathorn, Andrew, Torres, Katy, Wingo, Aliza P., Zai, Clement C., Aiello, Allison E., Almli, Lynn M., Amstadter, Ananda B., Andersen, Soren B., Andreassen, Ole A., Arbisi, Paul A., Ashley-Koch, Allison E., Austin, S. Bryn, Avdibegovic, Esmina, Borglum, Anders D., Babic, Dragan, Bækvad-Hansen, Marie, Baker, Dewleen G., Beckham, Jean C., Bierut, Laura J., Bisson, Jonathan I., Boks, Marco P., Bolger, Elizabeth A., Bradley, Bekh, Brashear, Meghan, Breen, Gerome, Bryant, Richard A., Bustamante, Angela C., Bybjerg-Grauholm, Jonas, Calabrese, Joseph R., Caldas-de-Almeida, Jose Miguel, Chen, Chia-Yen, Dale, Anders M., Dalvie, Shareefa, Deckert, Jürgen, Delahanty, Douglas L., Dennis, Michelle F., Disner, Seth G., Domschke, Katharina, Duncan, Laramie E., Kulenovic, Alma Dzubur, Erbes, Christopher R., Evans, Alexandra, Farrer, Lindsay A., Feeny, Norah C., Flory, Janine D., Forbes, David, Franz, Carol E., Galea, Sandro, Garrett, Melanie E., Gautam, Aarti, Gelaye, Bizu, Gelernter, Joel, Geuze, Elbert, Gillespie, Charles F., Uka, Aferdita Goci, Gordon, Scott D., Guffanti, Guia, Hammamieh, Rasha, Hauser, Michael A., Heath, Andrew C., Hemmings, Sian M.J., Hougaard, David Michael, Jakovljevic, Miro, Jett, Marti, Johnson, Eric Otto, Jones, Ian, Jovanovic, Tanja, Qin, Xue-Jun, Karstoft, Karen-Inge, Kaufman, Milissa L., Kessler, Ronald C., Khan, Alaptagin, Kimbrel, Nathan A., King, Anthony P., Koen, Nastassja, Kranzler, Henry R., Kremen, William S., Lawford, Bruce R., Lebois, Lauren A.M., Lewis, Catrin, Liberzon, Israel, Linnstaedt, Sarah D., Logue, Mark W., Lori, Adriana, Lugonja, Bozo, Luykx, Jurjen J., Lyons, Michael J., Maples-Keller, Jessica L., Marmar, Charles, Martin, Nicholas G., Maurer, Douglas, Mavissakalian, Matig R., McFarlane, Alexander, McGlinchey, Regina E., McLaughlin, Katie A., McLean, Samuel A., Mehta, Divya, Mellor, Rebecca, Michopoulos, Vasiliki, Milberg, William, Miller, Mark W., Morris, Charles Phillip, Mors, Ole, Mortensen, Preben Bo, Nelson, Elliot C., Nordentoft, Merete, Norman, Sonya B., O’Donnell, Meaghan, Orcutt, Holly K., Panizzon, Matthew S., Peters, Edward S., Peterson, Alan L., Peverill, Matthew, Pietrzak, Robert H., Polusny, Melissa A., Rice, John P., Risbrough, Victoria B., Roberts, Andrea L., Rothbaum, Alex O., Rothbaum, Barbara O., Roy-Byrne, Peter, Ruggiero, Kenneth J., Rung, Ariane, Rutten, Bart P.F., Saccone, Nancy L., Sanchez, Sixto E., Schijven, Dick, Seedat, Soraya, Seligowski, Antonia V., Seng, Julia S., Sheerin, Christina M., Silove, Derrick, Smith, Alicia K., Smoller, Jordan W., Sponheim, Scott R., Stein, Dan J., Stevens, Jennifer S., Teicher, Martin H., Thompson, Wesley K., Trapido, Edward, Uddin, Monica, Ursano, Robert J., Luella van den Heuvel, Leigh, Van Hooff, Miranda, Vermetten, Eric, Vinkers, Christiaan, Voisey, Joanne, Wang, Yunpeng, Wang, Zhewu, Werge, Thomas, Williams, Michelle A., Williamson, Douglas E., Winternitz, Sherry, Wolf, Christiane, Wolf, Erika J., Yehuda, Rachel, Young, Keith A., Young, Ross McD., Zhao, Hongyu, Zoellner, Lori A., Haas, Magali, Lasseter, Heather, Provost, Allison C., Salem, Rany M., Sebat, Jonathan, Shaffer, Richard, Wu, Tianying, Ripke, Stephan, Daly, Mark J., Ressler, Kerry J., Koenen, Karestan C., Stein, Murray B., Nievergelt, Caroline M., Wendt, Frank R., Garcia-Argibay, Miguel, Cabrera-Mendoza, Brenda, Valdimarsdóttir, Unnur A., Nivard, Michel G., Larsson, Henrik, Mattheisen, Manuel, and Meier, Sandra M.

Published
2023
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7. DNA sequencing in the classroom: complete genome sequence of two earwig (Dermaptera; Insecta) species

Author

Kobayashi, Sanae, Maldonado, Jonathan E., Gaete, Alexis, Araya, Ingrid, Aguado-Norese, Constanza, Cumplido, Nicolás, Díaz, Sebastián, Espinoza, Alonso, Fernández, Edelmira, Gajardo, Felipe, González-Ordenes, Felipe, Hauyon, Khantati, Maldonado, Piedad, Maldonado, Rodrigo, Pochet, Isabel, Riveros, Aníbal, Sandoval, Paula, Sepúlveda-González, Ailynne, Stuardo, Camila, Tapia-Reyes, Patricio, Thornton, Carolina, Undurraga, Soledad, Varas, Macarena, Valdivieso, Camilo, Phillips, Alan, Aros, Alejandro, Alarcón, Alexandra, Mendiboure, Alonso, Sepúlveda, Alyson, Zepeda, Amalia, Bustamante, Angela, Russu, Angelo, Martínez, Anselmo, Inostroza, Antonia, Palma, Antonio, Ponce, Bárbara, Báez, Belén, Dianta, Belén, Zenteno, Benjamín, Jelvez, Berenice, Henríquez, Brisa, Concha, Camila, Fuentes, Catalina, Morales, Catalina, Inostrosa, Claudia, Valenzuela, Claudio, Dercolto, Constanza, Malebrán, Cristian, González, Damián, Venegas, Daniel, Alvear, Dayhanne, Martínez, Deyna, Silva, Diana, Abarca, Diego, Fuentes, Elías, Inzunza, Elizabeth, Alfaro, Fabián, Aqueveque, Fernanda, Cartes, Fernanda, Delgado, Fernanda, Sandoval, Fernanda, Tamayo, Fernanda, Espinoza, Francisco, Espinoza, Gladys, Inzunza, Gonzalo, Vidal, Gonzalo, Roca, Grisel, Sánchez, Hileinn, Defaur, Jared, Sazo, Jonathan, Fuentes, José Manuel, Caéete, José Miguel, Vásquez, Juan Pablo, Reyes, Karin, Piéa, Karina, Orellana, Katherien, Vega, Lisandro, Lagos, Loreto, Ponce, Magdalena, Maldonado, Catalina, González, María Alejandra, Torres, María Ignacia, Irribarra, Mariana, Sanguinetti, Mariangela, Leiva, Mario, Ibacache, Marjorie, Yaéez, Martín, Palamara, Martina, Magnani, Massimo, Padilla, Maykol, Arancibia, Millaray, Acevedo, Milovan, Morales, Génesis, Castillo, Nallely, Carvajal, Nélida, González, Omar, Alvarado, Paola, Muéoz, Pía, Erazo, Renata, Silva, Rocío, Sepúlveda, Rodrigo, Valdés, Rodrigo, Molina, Ronny, Costa, Saraí, Alvear, Sebastián, Acuéa, Sofía, Mendoza, Sofía, Sáez, Sofia, Tapia, Sofía, Cerda, Tamara, Zamorano, Tomás, Araya, Valentina, Cortez, Valentina, Pereira, Valentina, Pino, Valentina, Yáéez, Victoria, Jaramillo, Viviana, Rivera, Yavanna, Urbina, Yerko, and Uzcátegui, Zuleimy

Published
2023
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13. The Relationship of Attention-Deficit/Hyperactivity Disorder With Posttraumatic Stress Disorder: A Two-Sample Mendelian Randomization and Population-Based Sibling Comparison Study

Author

Wendt, Frank R., primary, Garcia-Argibay, Miguel, additional, Cabrera-Mendoza, Brenda, additional, Valdimarsdóttir, Unnur A., additional, Gelernter, Joel, additional, Stein, Murray B., additional, Nivard, Michel G., additional, Maihofer, Adam X., additional, Nievergelt, Caroline M., additional, Larsson, Henrik, additional, Mattheisen, Manuel, additional, Polimanti, Renato, additional, Meier, Sandra M., additional, Choi, Karmel W., additional, Coleman, Jonathan R.I., additional, Daskalakis, Nikolaos P., additional, Denckla, Christy A., additional, Ketema, Elizabeth, additional, Morey, Rajendra A., additional, Ratanatharathorn, Andrew, additional, Torres, Katy, additional, Wingo, Aliza P., additional, Zai, Clement C., additional, Aiello, Allison E., additional, Almli, Lynn M., additional, Amstadter, Ananda B., additional, Andersen, Soren B., additional, Andreassen, Ole A., additional, Arbisi, Paul A., additional, Ashley-Koch, Allison E., additional, Austin, S. Bryn, additional, Avdibegovic, Esmina, additional, Borglum, Anders D., additional, Babic, Dragan, additional, Bækvad-Hansen, Marie, additional, Baker, Dewleen G., additional, Beckham, Jean C., additional, Bierut, Laura J., additional, Bisson, Jonathan I., additional, Boks, Marco P., additional, Bolger, Elizabeth A., additional, Bradley, Bekh, additional, Brashear, Meghan, additional, Breen, Gerome, additional, Bryant, Richard A., additional, Bustamante, Angela C., additional, Bybjerg-Grauholm, Jonas, additional, Calabrese, Joseph R., additional, Caldas-de-Almeida, Jose Miguel, additional, Chen, Chia-Yen, additional, Dale, Anders M., additional, Dalvie, Shareefa, additional, Deckert, Jürgen, additional, Delahanty, Douglas L., additional, Dennis, Michelle F., additional, Disner, Seth G., additional, Domschke, Katharina, additional, Duncan, Laramie E., additional, Kulenovic, Alma Dzubur, additional, Erbes, Christopher R., additional, Evans, Alexandra, additional, Farrer, Lindsay A., additional, Feeny, Norah C., additional, Flory, Janine D., additional, Forbes, David, additional, Franz, Carol E., additional, Galea, Sandro, additional, Garrett, Melanie E., additional, Gautam, Aarti, additional, Gelaye, Bizu, additional, Geuze, Elbert, additional, Gillespie, Charles F., additional, Uka, Aferdita Goci, additional, Gordon, Scott D., additional, Guffanti, Guia, additional, Hammamieh, Rasha, additional, Hauser, Michael A., additional, Heath, Andrew C., additional, Hemmings, Sian M.J., additional, Hougaard, David Michael, additional, Jakovljevic, Miro, additional, Jett, Marti, additional, Johnson, Eric Otto, additional, Jones, Ian, additional, Jovanovic, Tanja, additional, Qin, Xue-Jun, additional, Karstoft, Karen-Inge, additional, Kaufman, Milissa L., additional, Kessler, Ronald C., additional, Khan, Alaptagin, additional, Kimbrel, Nathan A., additional, King, Anthony P., additional, Koen, Nastassja, additional, Kranzler, Henry R., additional, Kremen, William S., additional, Lawford, Bruce R., additional, Lebois, Lauren A.M., additional, Lewis, Catrin, additional, Liberzon, Israel, additional, Linnstaedt, Sarah D., additional, Logue, Mark W., additional, Lori, Adriana, additional, Lugonja, Bozo, additional, Luykx, Jurjen J., additional, Lyons, Michael J., additional, Maples-Keller, Jessica L., additional, Marmar, Charles, additional, Martin, Nicholas G., additional, Maurer, Douglas, additional, Mavissakalian, Matig R., additional, McFarlane, Alexander, additional, McGlinchey, Regina E., additional, McLaughlin, Katie A., additional, McLean, Samuel A., additional, Mehta, Divya, additional, Mellor, Rebecca, additional, Michopoulos, Vasiliki, additional, Milberg, William, additional, Miller, Mark W., additional, Morris, Charles Phillip, additional, Mors, Ole, additional, Mortensen, Preben Bo, additional, Nelson, Elliot C., additional, Nordentoft, Merete, additional, Norman, Sonya B., additional, O’Donnell, Meaghan, additional, Orcutt, Holly K., additional, Panizzon, Matthew S., additional, Peters, Edward S., additional, Peterson, Alan L., additional, Peverill, Matthew, additional, Pietrzak, Robert H., additional, Polusny, Melissa A., additional, Rice, John P., additional, Risbrough, Victoria B., additional, Roberts, Andrea L., additional, Rothbaum, Alex O., additional, Rothbaum, Barbara O., additional, Roy-Byrne, Peter, additional, Ruggiero, Kenneth J., additional, Rung, Ariane, additional, Rutten, Bart P.F., additional, Saccone, Nancy L., additional, Sanchez, Sixto E., additional, Schijven, Dick, additional, Seedat, Soraya, additional, Seligowski, Antonia V., additional, Seng, Julia S., additional, Sheerin, Christina M., additional, Silove, Derrick, additional, Smith, Alicia K., additional, Smoller, Jordan W., additional, Sponheim, Scott R., additional, Stein, Dan J., additional, Stevens, Jennifer S., additional, Teicher, Martin H., additional, Thompson, Wesley K., additional, Trapido, Edward, additional, Uddin, Monica, additional, Ursano, Robert J., additional, Luella van den Heuvel, Leigh, additional, Van Hooff, Miranda, additional, Vermetten, Eric, additional, Vinkers, Christiaan, additional, Voisey, Joanne, additional, Wang, Yunpeng, additional, Wang, Zhewu, additional, Werge, Thomas, additional, Williams, Michelle A., additional, Williamson, Douglas E., additional, Winternitz, Sherry, additional, Wolf, Christiane, additional, Wolf, Erika J., additional, Yehuda, Rachel, additional, Young, Keith A., additional, Young, Ross McD., additional, Zhao, Hongyu, additional, Zoellner, Lori A., additional, Haas, Magali, additional, Lasseter, Heather, additional, Provost, Allison C., additional, Salem, Rany M., additional, Sebat, Jonathan, additional, Shaffer, Richard, additional, Wu, Tianying, additional, Ripke, Stephan, additional, Daly, Mark J., additional, Ressler, Kerry J., additional, and Koenen, Karestan C., additional

Published
2023
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14. Analysis of lumbar spine stenosis specimens for identification of amyloid

Author

Maurer, Mathew S., primary, Smiley, Dia, additional, Simsolo, Eli, additional, Remotti, Fabrizio, additional, Bustamante, Angela, additional, Teruya, Sergio, additional, Helmke, Stephen, additional, Einstein, Andrew J., additional, Lehman, Ronald, additional, Giles, Jon T., additional, Kelly, Jeffery W., additional, Tsai, Felix, additional, Blaner, William S., additional, Brun, Pierre‐Jacques, additional, Riesenburger, Ron I., additional, Kryzanski, James, additional, Varga, Cindy, additional, and Patel, Ayan R., additional

Published
2022
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15. Enhancing discovery of genetic variants for PTSD through integration of quantitative phenotypes and trauma exposure information

Author

Maihofer, Adam X., Choi, Karmel W., Coleman, Jonathan R.I., Daskalakis, Nikolaos P., Denckla, Christy A., Ketema, Elizabeth, Morey, Rajendra A., Polimanti, Renato, Ratanatharathorn, Andrew, Torres, Katy, Wingo, Aliza P., Zai, Clement C., Aiello, Allison E., Almli, Lynn M., Amstadter, Ananda B., Andersen, Soren B., Andreassen, Ole A., Arbisi, Paul A., Ashley-Koch, Allison E., Austin, S. Bryn, Avdibegovic, Esmina, Borglum, Anders D., Babic, Dragan, Bkvad-Hansen, Marie, Baker, Dewleen G., Beckham, Jean C., Bierut, Laura J., Bisson, Jonathan I., Boks, Marco P., Bolger, Elizabeth A., Bradley, Bekh, Brashear, Meghan, Breen, Gerome, Bryant, Richard A., Bustamante, Angela C., Bybjerg-Grauholm, Jonas, Calabrese, Joseph R., Caldas-de-Almeida, J.M., Chen, Chia-Yen, Dale, Anders M., Dalvie, Shareefa, Deckert, Jürgen, Delahanty, Douglas L., Dennis, Michelle F., Disner, Seth G., Domschke, Katharina, Duncan, Laramie E., Kulenovic, Alma Dzubur, Erbes, Christopher R., Evans, Alexandra, Farrer, Lindsay A., Feeny, Norah C., Flory, Janine D., Forbes, David, Franz, Carol E., Galea, Sandro, Garrett, Melanie E., Gautam, Aarti, Gelaye, Bizu, Gelernter, Joel, Geuze, Elbert, Gillespie, Charles F., Goci, Aferdita, Gordon, Scott D., Guffanti, Guia, Hammamieh, Rasha, Hauser, Michael A., Heath, Andrew C., Hemmings, Sian M.J., Hougaard, David Michael, Jakovljevic, Miro, Jett, Marti, Johnson, Eric Otto, Jones, Ian, Jovanovic, Tanja, Qin, Xue-Jun, Karstoft, Karen-Inge, Kaufman, Milissa L., Kessler, Ronald C., Khan, Alaptagin, Kimbrel, Nathan A., King, Anthony P., Koen, Nastassja, Kranzler, Henry R., Kremen, William S., Lawford, Bruce R., Lebois, Lauren A.M., Lewis, Catrin, Liberzon, Israel, Linnstaedt, Sarah D., Logue, Mark W., Lori, Adriana, Lugonja, Bozo, Luykx, Jurjen J., Lyons, Michael J., Maples-Keller, Jessica L., Marmar, Charles, Martin, Nicholas G., Maurer, D., Mavissakalian, Matig R., McFarlane, Alexander, McGlinchey, Regina E., McLaughlin, Katie A., McLean, Samuel A., Mehta, Divya, Mellor, Rebecca, Michopoulos, Vasiliki, Milberg, William, Miller, Mark W., Morris, Charles Phillip, Mors, Ole, Mortensen, P.B., Nelson, Elliot C., Nordentoft, Merete, Norman, Sonya B., O'Donnell, Meaghan, Orcutt, Holly K., Panizzon, Matthew S., Peters, Edward S., Peterson, Alan L., Peverill, Matthew, Pietrzak, Robert H., Polusny, Melissa A., Rice, John P., Risbrough, Victoria B., Roberts, Andrea L., Rothbaum, Alex O., Rothbaum, Barbara O., Roy-Byrne, P., Ruggiero, Kenneth J., Rung, Ariane, Rutten, Bart P.F., Saccone, Nancy L., Sanchez, Sixto E., Schijven, Dick, Seedat, S., Seligowski, Antonia V., Seng, Julia S., Sheerin, Christina M., Silove, Derrick, Smith, Alicia K., Smoller, Jordan W., Sponheim, Scott R., Stein, Dan J., Stevens, Jennifer S., Teicher, Martin H., Thompson, Wesley K., Trapido, Edward, Uddin, Monica, Ursano, Robert J., Luella van den Heuvel, Leigh, Van Hooff, Miranda, Vermetten, Eric, Vinkers, Christiaan, Voisey, Joanne, Wang, Yunpeng, Wang, Zhewu, Werge, Thomas, Williams, Michelle A., Williamson, Douglas E., Winternitz, Sherry, Wolf, Christiane, Wolf, Erika J., Yehuda, Rachel, Young, Keith A., Young, Ross McD., Zhao, Hongyu, Zoellner, Lori A., Haas, Magali, Lasseter, Heather, Provost, Allison C., Salem, Rany M., Sebat, Jonathan, Shaffer, Richard A., Wu, Tianying, Ripke, Stephan, Daly, Mark J., Ressler, Kerry J., Koenen, Karestan C., Stein, Murray B., and Nievergelt, Caroline M.

Subjects
trauma, mental disorders, PheWAS, GWAS, PTSD, genetics, heritability, behavioral disciplines and activities
Abstract

Background\ud Posttraumatic stress disorder (PTSD) is heritable and a potential consequence of exposure to traumatic stress. Evidence suggests that a quantitative approach to PTSD phenotype measurement and incorporation of lifetime trauma exposure (LTE) information could enhance the discovery power of PTSD genome-wide association studies (GWAS).\ud Methods\ud GWAS on PTSD symptoms was performed in 51 cohorts followed by a fixed-effects meta-analysis (N = 182,199 European Ancestry participants). A GWAS of LTE burden was performed in the UK Biobank cohort (N = 132,988). Genetic correlations were evaluated with LD-score regression. Multivariate analysis was performed using Multi-Trait Analysis of GWAS. Functional mapping and annotation of leading loci was performed with FUMA. Replication was evaluated using the Million Veteran Program (MVP) GWAS of PTSD total symptoms.\ud Results\ud GWAS of PTSD symptoms and LTE burden identified 5 and 6 independent genome-wide significant loci, respectively. There was a 72% genetic correlation between PTSD and LTE. PTSD and LTE showed largely similar patterns of genetic correlation with other traits, albeit with some distinctions. Adjusting PTSD for LTE reduced PTSD heritability by 31%. Multivariate analysis of PTSD and LTE increased the effective sample size of the PTSD GWAS by 20% and identified 4 additional loci. Four out of these 9 PTSD loci were independently replicated in MVP.\ud Conclusion\ud Through using a quantitative trait measure of PTSD, we identify novel risk loci not previously identified using prior case/control analyses. PTSD and LTE have a high genetic overlap that can be leveraged to increase discovery power through multivariate methods.

Published
2022

17. Genetics of PTSD

Author

Sumner, Jennifer A., additional, Bustamante, Angela C., additional, Koenen, Karestan C., additional, and Uddin, Monica, additional

Published
2016
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19. Correction: Corrigendum: DICER1 and microRNA regulation in post-traumatic stress disorder with comorbid depression

Author

Wingo, Aliza P., Almli, Lynn M., Stevens, Jennifer S., Klengel, Torsten, Uddin, Monica, Li, Yujing, Bustamante, Angela C., Lori, Adriana, Koen, Nastassja, Stein, Dan J., Smith, Alicia K., Aiello, Allison E., Koenen, Karestan C., Wildman, Derek E., Galea, Sandro, Bradley, Bekh, Binder, Elisabeth B., Jin, Peng, Gibson, Greg, and Ressler, Kerry J.

Published
2016
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20. Fluoride concentration in salt for human consumption available in a sample of markets and supermarkets in the district of Independencia, department of Lima, Peru, 2018

Author

Evangelista Carpio, Daniela Minerva, Tanaka Bustamante, Angela Yoshy, Pachas Barrionuevo, Flor de María, and Orejuela Ramírez, Francisco José

Subjects
purl.org/pe-repo/ocde/ford#2.11.01 [http], Prevención, Salud Bucal, Marcas de sal, Concentración de flúor, purl.org/pe-repo/ocde/ford#3.02.14 [http]
Abstract

Antecedentes: El control de calidad de la concentración de flúor en la sal de consumo humano, es una garantía de la disponibilidad de un micro elemento nutricional y además preventivo para disminuir la prevalencia de caries dental en la población. En Perú, las entidades responsables no efectúan este monitoreo. Objetivo: Determinar la concentración de fluoruros en sal de mesa de marcas comercializadas en el distrito de Independencia, departamento de Lima-Perú. Métodos y Materiales: Estudio descriptivo, transversal y observacional. La población está conformada por una base de datos con registros de la concentración de flúor de sal procedente de una muestra de conveniencia, de un total de 10 paquetes de 9 distintas marcas de sal de consumo humano captadas de diversos establecimientos autorizados (mercados y supermercados) entre Mayo-Junio 2018, como parte de una experiencia formativa de pregrado en el campo de salud pública bucal. Resultados: Solo el 36% de las marcas de sal comercializadas en el distrito de Independencia cumplieron con la Norma Técnica Peruana. Las marcas que estuvieron dentro del rango permitido fueron: Lobos, PuraSal, Bell’s, Metro. Conclusión: Se concluye que la población de Independencia está expuesta al consumo de sal fluorada con y sin las concentraciones óptimas. Background: Quality control of the concentration of fluoride in salt for human consumption is a guarantee of the availability of a nutritional microelement and also preventive to reduce the prevalence of dental caries in the population. In Peru, the responsible entities do not carry out this monitoring. Objective: Determinate the concentration of fluoride in salt of brands marketed in the district of Independencia, department of Lima-Peru. Methods and Materials: Descriptive, cross-sectional, observational study. The population consisted of a database with records of the fluoride concentration of salt from a convenience sample of a total of 10 packages of 9 different brands of salt for human consumption collected from various authorized establishments (markets and supermarkets) between May-June 2018. Results: Only 36% of the salt brands marketed in the district of Independencia complied with the Peruvian Technical Standard. The brands that were within the permitted range were: Lobos, PuraSal, Bell's, Metro. Conclusion: It is concluded that the population of Independencia is exposed to fluoridated salt consumption with and without optimal concentrations.

Published
2021

21. Supplement_Long-term survivors of murine sepsis are predisposed to enhanced LPS-induced lung injury and pro-inflammatory immune reprogramming

Author

Denstaedt, Scott, Bustamante, Angela C., W. Newstead, Michael, B. Moore, Bethany, J Standiford, Theodore, L Zemans, Rachel, and H. Singer, Benjamin

Subjects
respiratory system, respiratory tract diseases
Abstract

This data is supplemental to our study examining the long-term effects of sepsis on the lung in a murine model of post-sepsis LPS-induced lung injury. See original manuscript for details regarding methodology and approval.

Published
2021
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23. List of Contributors

Author

Abdolmaleky, Hamid Mostafavi, primary, Ambrosini, Alexander, additional, Avramopoulos, Dimitrios, additional, Bérubé, Nathalie G., additional, Bernacki, Carolyn, additional, Beveridge, Natalie J., additional, Bhat, Unis Ahmad, additional, Boks, Marco P.M., additional, Bongiorno, Charles, additional, Bustamante, Angela, additional, Chakravarty, Sumana, additional, Coppedè, Fabio, additional, Dong, Erbo, additional, Elia, Josephine, additional, Franklin, Tamara Brook, additional, Grayson, Dennis R., additional, Gropman, Andrea L., additional, Guidotti, Alessandro, additional, Gupta, Praveer, additional, Hakonarson, Hakon, additional, Hing, Benjamin, additional, Hunter, Richard G., additional, Imamura, Takuya, additional, Kaminsky, Zachary A., additional, Kingsley, Richard, additional, Kramer, Jamie M., additional, Kumar, Arvind, additional, Kundakovic, Marija, additional, Labonté, Benoit, additional, Lee, Richard, additional, Lutz, Pierre-Eric, additional, Manev, Hari, additional, Matt, Stephanie, additional, Maze, Ian, additional, McGowan, Patrick O., additional, Murgatroyd, Chris, additional, Nakashima, Kinichi, additional, Okuyama, Makiko, additional, Paul, Bidisha, additional, Peedicayil, Jacob, additional, Potash, James B., additional, Reddy, R Gajendra, additional, Roth, Eric D., additional, Roth, Tania L., additional, Sasaki, Aya, additional, Schoenrock, Sarah Adams, additional, Shinozaki, Gen, additional, Tarantino, Lisa M., additional, Thiagalingam, Sam, additional, Tollefsbol, Trygve O., additional, Toyokawa, Satoshi, additional, Turecki, Gustavo, additional, Uddin, Monica, additional, Uesaka, Masahiro, additional, Wenderski, Wendy, additional, Yamamoto, Naoki, additional, and Yost, Oliver, additional

Published
2014
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25. Transcriptomic Profiles of Sepsis in the Human Brain

Author

Bustamante, Angela C., primary, Opron, Kristopher, additional, Ehlenbach, William J., additional, Larson, Eric B., additional, Crane, Paul K., additional, Keene, C. Dirk, additional, Standiford, Theodore J., additional, and Singer, Benjamin H., additional

Published
2020
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27. Association of Economic Status and Educational Attainment With Posttraumatic Stress Disorder: A Mendelian Randomization Study

Author

Polimanti, Renato, Ratanatharathorn, Andrew, Maihofer, Adam X., Choi, Karmel W., Stein, Murray B., Morey, Rajendra A., Logue, Mark W., Nievergelt, Caroline M., Stein, Dan J., Koenen, Karestan C., Gelernter, Joel, Klengel, Torsten, Atkinson, Elizabeth G., Chen, Chia-Yen, Coleman, Jonathan R. I., Dalvie, Shareefa, Duncan, Laramie E., Provost, Allison C., Torres, Katy, Aiello, Allison E., Almli, Lynn M., Amstadter, Ananda B., Andersen, Soren B., Andreassen, Ole A., Arbisi, Paul A., Ashley-Koch, Allison E., Austin, S. Bryn, Avdibegovic, Esmina, Babic, Dragan, Baekvad-Hansen, Marie, Baker, Dewleen G., Beckham, Jean C., Bierut, Laura J., Bisson, Jonathan I., Boks, Marco P., Bolger, Elizabeth A., Borglum, Anders D., Bradley, Bekh, Brashear, Megan, Breen, Gerome, Bryant, Richard A., Bustamante, Angela C., Bybjerg-Grauholm, Jonas, Calabrese, Joseph R., Rutten, Bart P. F., MUMC+: MA Psychiatrie (3), Psychiatrie & Neuropsychologie, and RS: MHeNs - R3 - Neuroscience

Subjects
Linkage disequilibrium, Cross-sectional study, DIVERSITY, Polymorphism, Single Nucleotide, Stress Disorders, Post-Traumatic, 03 medical and health sciences, Cognition, Risk-Taking, 0302 clinical medicine, GENETIC-VARIANTS, Mendelian randomization, SCHIZOPHRENIA, medicine, Economic Status, Humans, RNA-SEQ, Socioeconomic status, Original Investigation, 030304 developmental biology, Genetic association, Psychiatry, RISK, 0303 health sciences, business.industry, Research, Mendelian Randomization Analysis, PTSD, General Medicine, Explained variation, medicine.disease, COGNITIVE-ABILITY, Online Only, Cross-Sectional Studies, Schizophrenia, Educational Status, TRAJECTORIES, business, 030217 neurology & neurosurgery, Clinical psychology
Abstract

Key Points Question Which mechanisms underlie the negative association of posttraumatic stress disorder (PTSD) with traits related to educational attainment (EA)? Findings In this mendelian randomization study based on large-scale genomic data sets, including data from more than 1 million individuals, EA was negatively associated with PTSD, also supporting the role of economic status as a mediator in this association. Meaning This study suggests that economic status may mediate the association of EA with PTSD independent of the brain mechanisms associated with EA., This mendelian randomization study investigates the association of posttraumatic stress disorder and traits associated with educational attainment., Importance There is a well-established negative association of educational attainment (EA) and other traits related to cognitive ability with posttraumatic stress disorder (PTSD), but the underlying mechanisms are poorly understood. Objectives To investigate the association of PTSD with traits related to EA. Design, Setting, and Participants Genetic correlation, polygenic risk scoring, and mendelian randomization (MR) were conducted including 23 185 individuals with PTSD and 151 309 control participants from the Psychiatric Genomics Consortium for PTSD and up to 1 131 881 individuals assessed for EA and related traits from UK Biobank, 23andMe, and the Social Science Genetic Association Consortium. Data were analyzed from July 3 through November 19, 2018. Main Outcomes and Measures Genetic correlation obtained from linkage disequilibrium score regression, phenotypic variance explained by polygenic risk scores, and association estimates from MR. Results Summary association data from multiple genome-wide association studies were available for a total of 1 180 352 participants (634 391 [53.7%] women). Posttraumatic stress disorder showed negative genetic correlations with EA (rg = −0.26; SE = 0.05; P = 4.60 × 10−8). Mendelian randomization analysis, conducting considering a random-effects inverse-variance weighted method, indicated that EA has a negative association with PTSD (β = −0.23; 95% CI, −0.07 to −0.39; P = .004). Investigating potential mediators of the EA-PTSD association, propensity for trauma exposure and risk-taking behaviors were observed as risk factors for PTSD independent of EA (trauma exposure: β = 0.37; 95% CI, 0.19 to 0.52; P = 2.57 × 10−5; risk-taking: β = 0.76; 95% CI, 0.38 to 1.13; P = 1.13 × 10−4), while income may mediate the association of EA with PSTD (MR income: β = −0.18; 95% CI, −0.29 to −0.07; P = .001; MR EA: β = −0.23; 95% CI, −0.39 to −0.07; P = .004; multivariable MR income: β = −0.32; 95% CI, −0.57 to 0.07; P = .02; multivariable MR EA: β = −0.04; 95% CI, −0.29 to 0.21; SE, 0.13; P = .79). Conclusions and Relevance Large-scale genomic data sets add further evidence to the negative association of EA with PTSD, also supporting the role of economic status as a mediator in the association observed.

Published
2019

29. Largest genome-wide association study for PTSD identifies genetic risk loci in European and African ancestries and implicates novel biological pathways

Author

Nievergelt, Caroline M., primary, Maihofer, Adam X., additional, Klengel, Torsten, additional, Atkinson, Elizabeth G., additional, Chen, Chia-Yen, additional, Choi, Karmel W., additional, Coleman, Jonathan R.I., additional, Dalvie, Shareefa, additional, Duncan, Laramie E., additional, Logue, Mark W., additional, Provost, Allison C., additional, Ratanatharathorn, Andrew, additional, Stein, Murray B., additional, Torres, Katy, additional, Aiello, Allison E., additional, Almli, Lynn M., additional, Amstadter, Ananda B., additional, Andersen, Søren B, additional, Andreassen, Ole A., additional, Arbisi, Paul A., additional, Ashley-Koch, Allison E., additional, Austin, S. Bryn, additional, Avdibegovic, Esmina, additional, Babić, Dragan, additional, Bækvad-Hansen, Marie, additional, Baker, Dewleen G., additional, Beckham, Jean C., additional, Bierut, Laura J., additional, Bisson, Jonathan I., additional, Boks, Marco P., additional, Bolger, Elizabeth A., additional, Børglum, Anders D., additional, Bradley, Bekh, additional, Brashear, Megan, additional, Breen, Gerome, additional, Bryant, Richard A., additional, Bustamante, Angela C., additional, Bybjerg-Grauholm, Jonas, additional, Calabrese, Joseph R., additional, Caldas-de-Almeida, José M., additional, Dale, Anders M., additional, Daly, Mark J., additional, Daskalakis, Nikolaos P., additional, Deckert, Jürgen, additional, Delahanty, Douglas L., additional, Dennis, Michelle F., additional, Disner, Seth G., additional, Domschke, Katharina, additional, Dzubur-Kulenovic, Alma, additional, Erbes, Christopher R., additional, Evans, Alexandra, additional, Farrer, Lindsay A., additional, Feeny, Norah C., additional, Flory, Janine D., additional, Forbes, David, additional, Franz, Carol E., additional, Galea, Sandro, additional, Garrett, Melanie E., additional, Gelaye, Bizu, additional, Gelernter, Joel, additional, Geuze, Elbert, additional, Gillespie, Charles, additional, Goci Uka, Aferdita, additional, Gordon, Scott D., additional, Guffanti, Guia, additional, Hammamieh, Rasha, additional, Harnal, Supriya, additional, Hauser, Michael A., additional, Heath, Andrew C., additional, Hemmings, Sian M.J., additional, Michael Hougaard, David, additional, Jakovljevic, Miro, additional, Jett, Marti, additional, Otto Johnson, Eric, additional, Jones, Ian, additional, Jovanovic, Tanja, additional, Qin, Xue-Jun, additional, Junglen, Angela G., additional, Karstoft, Karen-Inge, additional, Kaufman, Milissa L., additional, Kessler, Ronald C., additional, Khan, Alaptagin, additional, Kimbrel, Nathan A., additional, King, Anthony P., additional, Koen, Nastassja, additional, Kranzler, Henry R., additional, Kremen, William S., additional, Lawford, Bruce R., additional, Lebois, Lauren A.M., additional, Lewis, Catrin E., additional, Linnstaedt, Sarah D., additional, Lori, Adriana, additional, Lugonja, Bozo, additional, Luykx, Jurjen J., additional, Lyons, Michael J., additional, Maples-Keller, Jessica, additional, Marmar, Charles, additional, Martin, Alicia R., additional, Martin, Nicholas G., additional, Maurer, Douglas, additional, Mavissakalian, Matig R., additional, McFarlane, Alexander, additional, McGlinchey, Regina E., additional, McLaughlin, Katie A., additional, McLean, Samuel A., additional, McLeay, Sarah, additional, Mehta, Divya, additional, Milberg, William P., additional, Miller, Mark W., additional, Morey, Rajendra A., additional, Phillip Morris, Charles, additional, Mors, Ole, additional, Mortensen, Preben B., additional, Neale, Benjamin M., additional, Nelson, Elliot C., additional, Nordentoft, Merete, additional, Norman, Sonya B., additional, O’Donnell, Meaghan, additional, Orcutt, Holly K., additional, Panizzon, Matthew S., additional, Peters, Edward S., additional, Peterson, Alan L., additional, Peverill, Matthew, additional, Pietrzak, Robert H., additional, Polusny, Melissa A., additional, Rice, John P., additional, Ripke, Stephan, additional, Risbrough, Victoria B., additional, Roberts, Andrea L., additional, Rothbaum, Alex O., additional, Rothbaum, Barbara O., additional, Roy-Byrne, Peter, additional, Ruggiero, Ken, additional, Rung, Ariane, additional, Rutten, Bart P. F., additional, Saccone, Nancy L., additional, Sanchez, Sixto E., additional, Schijven, Dick, additional, Seedat, Soraya, additional, Seligowski, Antonia V., additional, Seng, Julia S., additional, Sheerin, Christina M., additional, Silove, Derrick, additional, Smith, Alicia K., additional, Smoller, Jordan W., additional, Solovieff, Nadia, additional, Sponheim, Scott R., additional, Stein, Dan J., additional, Sumner, Jennifer A., additional, Teicher, Martin H., additional, Thompson, Wesley K., additional, Trapido, Edward, additional, Uddin, Monica, additional, Ursano, Robert J., additional, van den Heuvel, Leigh Luella, additional, van Hooff, Miranda, additional, Vermetten, Eric, additional, Vinkers, Christiaan H., additional, Voisey, Joanne, additional, Wang, Yunpeng, additional, Wang, Zhewu, additional, Werge, Thomas, additional, Williams, Michelle A., additional, Williamson, Douglas E., additional, Winternitz, Sherry, additional, Wolf, Christiane, additional, Wolf, Erika J., additional, Wolff, Jonathan D., additional, Yehuda, Rachel, additional, Young, Keith A., additional, Young, Ross McD., additional, Zhao, Hongyu, additional, Zoellner, Lori A., additional, Liberzon, Israel, additional, Ressler, Kerry J., additional, Haas, Magali, additional, and Koenen, Karestan C., additional

Published
2018
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32. DICER1 and microRNA regulation in post-traumatic stress disorder with comorbid depression

Author

Galea, Sandro, Bustamante, Angela C., Koenen, Karestan C., Klengel, Torsten, Wildman, Derek E., Gibson, Greg, Aiello, Allison E., Jin, Peng, Bradley, Bekh, Koen, Nastassja, Stein, Dan J., Binder, Elisabeth B., Ressler, Kerry J., Lori, Adriana, Uddin, Monica, Li, Yujing, and Smith, Alicia K.

Subjects
mental disorders
Abstract

DICER1 is an enzyme that generates mature microRNAs (miRNAs), which regulate gene expression post-transcriptionally in brain and other tissues and is involved in synaptic maturation and plasticity. Here, through genome-wide differential gene expression survey of post-traumatic stress disorder (PTSD) with comorbid depression (PTSD&Dep), we find that blood DICER1 expression is significantly reduced in cases versus controls, and replicate this in two independent cohorts. Our follow-up studies find that lower blood DICER1 expression is significantly associated with increased amygdala activation to fearful stimuli, a neural correlate for PTSD. Additionally, a genetic variant in the 3′ un-translated region of DICER1, rs10144436, is significantly associated with DICER1 expression and with PTSD&Dep, and the latter is replicated in an independent cohort. Furthermore, genome-wide differential expression survey of miRNAs in blood in PTSD&Dep reveals miRNAs to be significantly downregulated in cases versus controls. Together, our novel data suggest DICER1 plays a role in molecular mechanisms of PTSD&Dep through the DICER1 and the miRNA regulation pathway.

Published
2015
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34. DICER1 and microRNA regulation in post-traumatic stress disorder with comorbid depression

Author

Wingo, Aliza P., primary, Almli, Lynn M., additional, Stevens, Jennifer S., additional, Klengel, Torsten, additional, Uddin, Monica, additional, Li, Yujing, additional, Bustamante, Angela C., additional, Lori, Adriana, additional, Koen, Nastassja, additional, Stein, Dan J., additional, Smith, Alicia K., additional, Aiello, Allison E., additional, Koenen, Karestan C., additional, Wildman, Derek E., additional, Galea, Sandro, additional, Bradley, Bekh, additional, Binder, Elisabeth B., additional, Jin, Peng, additional, Gibson, Greg, additional, and Ressler, Kerry J., additional

Published
2015
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38. La psicología evolutiva en la escuela soviética

Author

de Bustamante, Angela

Abstract

En la Psicología Evolutiva Soviética, el problema de las relaciones entre aprendizaje y desarrollo ocupa un lugar central. Este problema esta abordado desde el planteamiento teórico de Vygotski y su teoría histórico cultural. Los autores soviéticos sitúan como base fundamental del desarrollo la educación en su forma activa, es decir, el aprendizaje como proceso activo de asimilación de conocimientos. Para la Psicología Soviética la distinción entre factores que dependen de la maduración y factores que dependen del aprendizaje es insustancial e impide el estudio de las verdaderas leyes del desarrollo intelectual. Se rechaza el concepto evolutivo del desarrollo infantil. La división de la infancia en diferentes períodos se hace en base a la actividad rectora, es decir, la actividad que ocupa el centro de cada etapa alrededor de la cual gira la conducta del niño. La determinación de este tipo de actividad rectora, junto con la afirmación de que el aprendizaje es la base del desarrollo intelectual, constituyen los dos grandes pilares de investigación de la Psicología Infantil Soviética. Por eso los métodos que utilizan los psicólogos son siempre de carácter formativo.

Published
1978
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39. Corrigendum: DICER1 and microRNA regulation in post-traumatic stress disorder with comorbid depression.

Author

Wingo, Aliza P., Almli, Lynn M., Stevens, Jennifer S., Klengel, Torsten, Uddin, Monica, Li, Yujing, Bustamante, Angela C., Lori, Adriana, Koen, Nastassja, Stein, Dan J., Smith, Alicia K., Aiello, Allison E., Koenen, Karestan C., Wildman, Derek E., Galea, Sandro, Bradley, Bekh, Binder, Elisabeth B., Jin, Peng, Gibson, Greg, and Ressler, Kerry J.

Published
2016
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40. Discovery of 95 PTSD loci provides insight into genetic architecture and neurobiology of trauma and stress-related disorders.

Author

Nievergelt CM, Maihofer AX, Atkinson EG, Chen CY, Choi KW, Coleman JR, Daskalakis NP, Duncan LE, Polimanti R, Aaronson C, Amstadter AB, Andersen SB, Andreassen OA, Arbisi PA, Ashley-Koch AE, Austin SB, Avdibegoviç E, Babic D, Bacanu SA, Baker DG, Batzler A, Beckham JC, Belangero S, Benjet C, Bergner C, Bierer LM, Biernacka JM, Bierut LJ, Bisson JI, Boks MP, Bolger EA, Brandolino A, Breen G, Bressan RA, Bryant RA, Bustamante AC, Bybjerg-Grauholm J, Bækvad-Hansen M, Børglum AD, Børte S, Cahn L, Calabrese JR, Caldas-de-Almeida JM, Chatzinakos C, Cheema S, Clouston SAP, Colodro-Conde L, Coombes BJ, Cruz-Fuentes CS, Dale AM, Dalvie S, Davis LK, Deckert J, Delahanty DL, Dennis MF, deRoon-Cassini T, Desarnaud F, DiPietro CP, Disner SG, Docherty AR, Domschke K, Dyb G, Kulenovic AD, Edenberg HJ, Evans A, Fabbri C, Fani N, Farrer LA, Feder A, Feeny NC, Flory JD, Forbes D, Franz CE, Galea S, Garrett ME, Gelaye B, Gelernter J, Geuze E, Gillespie CF, Goci A, Goleva SB, Gordon SD, Grasser LR, Guindalini C, Haas M, Hagenaars S, Hauser MA, Heath AC, Hemmings SM, Hesselbrock V, Hickie IB, Hogan K, Hougaard DM, Huang H, Huckins LM, Hveem K, Jakovljevic M, Javanbakht A, Jenkins GD, Johnson J, Jones I, Jovanovic T, Karstoft KI, Kaufman ML, Kennedy JL, Kessler RC, Khan A, Kimbrel NA, King AP, Koen N, Kotov R, Kranzler HR, Krebs K, Kremen WS, Kuan PF, Lawford BR, Lebois LAM, Lehto K, Levey DF, Lewis C, Liberzon I, Linnstaedt SD, Logue MW, Lori A, Lu Y, Luft BJ, Lupton MK, Luykx JJ, Makotkine I, Maples-Keller JL, Marchese S, Marmar C, Martin NG, MartÍnez-Levy GA, McAloney K, McFarlane A, McLaughlin KA, McLean SA, Medland SE, Mehta D, Meyers J, Michopoulos V, Mikita EA, Milani L, Milberg W, Miller MW, Morey RA, Morris CP, Mors O, Mortensen PB, Mufford MS, Nelson EC, Nordentoft M, Norman SB, Nugent NR, O'Donnell M, Orcutt HK, Pan PM, Panizzon MS, Pathak GA, Peters ES, Peterson AL, Peverill M, Pietrzak RH, Polusny MA, Porjesz B, Powers A, Qin XJ, Ratanatharathorn A, Risbrough VB, Roberts AL, Rothbaum BO, Rothbaum AO, Roy-Byrne P, Ruggiero KJ, Rung A, Runz H, Rutten BPF, de Viteri SS, Salum GA, Sampson L, Sanchez SE, Santoro M, Seah C, Seedat S, Seng JS, Shabalin A, Sheerin CM, Silove D, Smith AK, Smoller JW, Sponheim SR, Stein DJ, Stensland S, Stevens JS, Sumner JA, Teicher MH, Thompson WK, Tiwari AK, Trapido E, Uddin M, Ursano RJ, Valdimarsdóttir U, van den Heuvel LL, Van Hooff M, van Rooij SJ, Vermetten E, Vinkers CH, Voisey J, Wang Z, Wang Y, Waszczuk M, Weber H, Wendt FR, Werge T, Williams MA, Williamson DE, Winsvold BS, Winternitz S, Wolf EJ, Wolf C, Xia Y, Xiong Y, Yehuda R, Young RM, Young KA, Zai CC, Zai GC, Zervas M, Zhao H, Zoellner LA, Zwart JA, Stein MB, Ressler KJ, and Koenen KC

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., 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.

Published
2023
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41. Long-term survivors of murine sepsis are predisposed to enhanced LPS-induced lung injury and proinflammatory immune reprogramming.

Author

Denstaedt SJ, Bustamante AC, Newstead MW, Moore BB, Standiford TJ, Zemans RL, and Singer BH

Subjects
Animals, Calgranulin A immunology, Calgranulin B immunology, Female, Humans, Inflammation chemically induced, Inflammation immunology, Inflammation pathology, Lung Injury chemically induced, Lung Injury pathology, Male, Mice, Monocytes immunology, Monocytes pathology, Sepsis chemically induced, Sepsis pathology, Tumor Necrosis Factor-alpha immunology, Lipopolysaccharides toxicity, Lung Injury immunology, Sepsis immunology
Abstract

Millions of people who survive sepsis each year are rehospitalized and die due to late pulmonary complications. To prevent and treat these complications, biomarkers and molecular mediators must be identified. Persistent immune reprogramming in the form of immunoparalysis and impaired host defense is proposed to mediate late pulmonary complications after sepsis, particularly new pulmonary infections. However, immune reprogramming may also involve enhanced/primed responses to secondary stimuli, although their contribution to long-term sepsis complications remains understudied. We hypothesize that enhanced/primed immune responses in the lungs of sepsis survivors are associated with late pulmonary complications. To this end, we developed a murine sepsis model using cecal ligation and puncture (CLP) followed 3 wk later by administration of intranasal lipopolysaccharide to induce inflammatory lung injury. Mice surviving sepsis exhibit enhanced lung injury with increased alveolar permeability, neutrophil recruitment, and enhanced Ly6C hi monocyte Tnf expression. To determine the mediators of enhanced lung injury, we performed flow cytometry and RNA sequencing of lungs 3 wk after CLP, prior to lipopolysaccharide. Sepsis survivor mice showed expanded Ly6C hi monocytes populations and increased expression of many inflammatory genes. Of these, S100A8/A9 was also elevated in the circulation of human sepsis survivors for months after sepsis, validating our model and identifying S100A8/A9 as a potential biomarker and therapeutic target for long-term pulmonary complications after sepsis. These data provide new insight into the importance of enhanced/primed immune responses in survivors of sepsis and establish a foundation for additional investigation into the mechanisms mediating this response.

Published
2021
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