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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, Maihofer, Adam, Atkinson, Elizabeth, Chen, Chia-Yen, Choi, Karmel, Coleman, Jonathan, Daskalakis, Nikolaos, Duncan, Laramie, Polimanti, Renato, Aaronson, Cindy, Amstadter, Ananda, Andersen, Soren, Andreassen, Ole, Arbisi, Paul, Ashley-Koch, Allison, Austin, S, Avdibegoviç, Esmina, Babić, Dragan, Bacanu, Silviu-Alin, Baker, Dewleen, Batzler, Anthony, Beckham, Jean, Belangero, Sintia, Benjet, Corina, Bergner, Carisa, Bierer, Linda, Biernacka, Joanna, Bierut, Laura, Bisson, Jonathan, Boks, Marco, Bolger, Elizabeth, Brandolino, Amber, Breen, Gerome, Bressan, Rodrigo, Bryant, Richard, Bustamante, Angela, Bybjerg-Grauholm, Jonas, Bækvad-Hansen, Marie, Børglum, Anders, Børte, Sigrid, Cahn, Leah, Calabrese, Joseph, Caldas-de-Almeida, Jose, Chatzinakos, Chris, Cheema, Sheraz, Clouston, Sean, Colodro-Conde, Lucía, Coombes, Brandon, Cruz-Fuentes, Carlos, Dale, Anders, Dalvie, Shareefa, Davis, Lea, Deckert, Jürgen, Delahanty, Douglas, Dennis, Michelle, Desarnaud, Frank, DiPietro, Christopher, Disner, Seth, Docherty, Anna, Domschke, Katharina, Dyb, Grete, Kulenović, Alma, Edenberg, Howard, Evans, Alexandra, Fabbri, Chiara, Fani, Negar, Farrer, Lindsay, Feder, Adriana, Feeny, Norah, Flory, Janine, Forbes, David, Franz, Carol, Galea, Sandro, Garrett, Melanie, Gelaye, Bizu, Gelernter, Joel, Geuze, Elbert, Gillespie, Charles, Goleva, Slavina, Gordon, Scott, Goçi, Aferdita, Grasser, Lana, Guindalini, Camila, Haas, Magali, Hagenaars, Saskia, Hauser, Michael, Heath, Andrew, Hemmings, Sian, Hesselbrock, Victor, Hickie, Ian, Hogan, Kelleigh, Hougaard, David, Huang, Hailiang, Huckins, Laura, Hveem, Kristian, Jakovljević, Miro, Javanbakht, Arash, Jenkins, Gregory, Johnson, Jessica, and Jones, Ian

Subjects
Humans, Genetic Loci, Genetic Predisposition to Disease, Genome-Wide Association Study, Neurobiology, Polymorphism, Single Nucleotide, Stress Disorders, Post-Traumatic, White People, White, Black or African American, American Indian or Alaska Native
Abstract

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.

Published
2024

2. 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

3. 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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4. 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 Mc D., 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., Koenen, Karestan C., 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 Mc D., 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.

Abstract

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., 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.

Published
2024

5. Symposia

Author

Correll, Christoph, Kutcher, Stanley P., McClellan, John, Buitelaar, Jan, Pappadopulos, Elizabeth, Rothenberger, Aribert, Mattejat, Fritz, Scott, Stephen, Weisz, John, Schulz, Eberhard, Felder, Wilhelm, Fleischhaker, Christian, Böhme, R., Sixt, B., Jan van der Gaag, Rutger, Katz, Laurence Y., Cox, Brian J., Gunasekara, Shiny, Miller, Alec L., Laor, Nathaniel, Riedesser, Peter, Caffo, Ernesto, Leckman, James, Ammaniti, Massimo, Nicolais, Giampaolo, Speranza, Mario, Steiner, Hans, Delizonna, Laura, Schallauer, Astrid, Thienemann, Margo, McFarlane, Alexander C., van Hooff, Miranda, Sawyer, Michael, Cianchetti, Carlo, Gaddour, Naoufel, Sana, Mokni, Anouar, Mechri, Mondher, Letaief, Lotfi, Gaha, Härtling, Fabian, Bittner, Robert, Haenschel, Corinna, Cap, Marcus, Goncharova, Tanja, Linden, David E. J., Dittmann, Ralf, Maestele, Anneliese, Mehler, Claudia, Meyer, Eberhard, Jenner, Jack A., Boeing, Leonie, Murray, Val, Pelosi, Anthony, McCabe, Robert, Blackwood, Douglas, Wrate, Robert, Pellerano, S., Pintor, M., Mellis, G. L., Piroddi, T., Flisher, Alan, Nesa, Monique, Rooney, Rosanna, Roberts, Clare, Kane, Robert, Silburn, Sven, Pike, Lisbeth, Deaton, Helge Staby, Lustig, Stuart, Funk, Michelle, Rickards, Anne, Reddihough, Dinah, Wright-Rossi, Roslyn, Simpson, Jacqui, Seuthe, Dieter David, Vielhaber, H., Orden, Kinderklinik Dritter, Backmund, H., Gerlinghoff, M., Schwab-Stone, Mary, Jespers, Ine, Vermeiren, Robert, Ruchkin, Vladislav, Blatny, Marek, Hrdlicka, Michal, Urbanek, Tomas, Jelinek, Martin, Balastikova, Veronika, Jeammet, Philippe, Frottin, Alain, Filipovic, Andjelka, Albert, Eric, Schelotto, Dora Musetti, Knezevic, Mladen, Jovancevic, Milivoj, Hill, Jonathan, Lawlor, Maria, Kienbacher, Christian, Prause, Carolin, Stöckl, Margit, Bogyi, Gertrude, Friedrich, Max H., Klein, Michael, Kürschner, Katrin, Murray, Lynne, Leidecker, Victoria, Sharp, Helen, Luoma, Ilona, Kaukonen, Pälvi, Tamminen, Tuula, Nurcombe, Barry, Martin, Graham, McDermott, Brett, Resch, Franz, Schimmelman, Benno Graf, Edwards, Jane, McGorry, Patrick D., Lambert, Martin, Conus, Philippe, Preuss, Ulrich, Bürgin, Dieter, Strauss, Monika, Parzer, Peter, Spiel, Georg, von Korff, C., Ballin, H.-A., Gößler, R., Günter, M., Sange, G., Meng, Heiner, Koch, Eginhard, Minde, Klaus, True, Mary, Pisani, L., Oumar, F., Padilla, J., Bouville, Jean-François, Vogel, Wendy, Schmeck, Klaus, Goth, Kirstin, Purper-Ouakil, Diane, Dessons, Véronique, Doyen, Catherine, Perez-Diaz, Fernando, Mouren-Simeoni, Marie-Christine, Karwautz, Andreas, Wagner, Gudrun, Schwienbacher, Klaus, Haidvogl, Maria, Nobis, Gerald, Treasure, Janet Linda, Collier, David Andrew, Brunner, Romuald, Hueg, A., Haffner, Johann, Schmid, Marc, Goldbeck, Lutz, Nützel, Jakob, Höfling, Volkmar, Schermelleh-Engel, Karin, Moosbrugger, Helfried, Tomàs, Josep, Cornellà, Josep, Llusent, Alex, Bielsa, Anna, Belfer, Myron, Robertson, Brian, Mandlhate, Custodia, Seck, Birama, Zwirs, Barbara, Burger, Huib, Schulpen, Tom, Salman Al-Obedy, A. Karem, Romanchuk, Oleh, Namyslowska, Irena, Reigstad, Björn S., Jorgensen, Kirsti Margrethe, Matthys, Walter, Lochman, John, Zonnevylle-Bender, Marjo, van de Wiel, Nicolle, Wagner, Angela, Jennen-Steinmetz, Christine, Goepel, Christopher, van Bokhoven, Irene, van Goozen, Stephanie, Franciosi, L. Patt, Acquoy, Leode Graaf, Tischlinger, Anne, Pharm, B., Bronder, Knut Halyard, Schleimer, Kari, Walter, Joachim, Ephraime, Boia, Dmitrieva, Tatjana, Silva, Alvaro Seligman, Becker, Katja, Steinhausen, Hans-Christoph, Metzke, C. Winkler, Furtado, Erikson F., Laucht, Manfred, Bilke, Oliver, Zimmermann, Petra, Wittchen, Hans-Ulrich, Lieb, Roselind, Hannesdottir, Helga, Tyrfingsson, Thorarinn, Döpfner, Manfred, Hahlweg, Kurt, Kuschel, Annett, Bertram, Heike, Heinrichs, Nina, Freund-Braier, Inez, Brix, Gabriele, Hautmann, Christopher, Pluck, Julia, Crijnen, Alfons, van Lier, Pol, Vuijk, Patricia, Frank, Reiner, Vandvik, Inger Helene, Schäfert, Rainer, van Weel, Jeanne, Schieveld, Jan, Fegert, Jörg M., Friedrich, William, Celestin-Westreich, Smadar, Celestin, Leon Patrice, Ponjaert-Kristoffersen, Ingrid, Nagao, Keizo, Kisida, M., Shindo, E., Larsen, Helmer Baying, Helweg-Larsen, Karin, Lindauer, Ramón, Booij, Jan, Olff, Miranda, den Heeten, Gerard, Gersons, Berthold, Boer, Frits, Schoentjes, Eric, Bal, Sarah, Schulte-Markwort, Michael, Solantaus, Tytti, Toikka, Sini, Alasuutari, Maarit, Steck, Barbara, Grether, Andrea, Ehrensperger, M., Amsler, Felix, Kappos, L., Saha, Rina, Paschen, Bela, Baldus, Christiane, Haagen, Miriam, Pott, Martina, Romer, Georg, Ono, Yoshiro, Homma, H., Ishida, Y., Ide, H., Okamoto, M., Kameoka, S., Nakayama, Hiroshi, Yamamoto, A., Mukaddes, Nahit Motavalli, Tyano, Sam, Mozes, Tamar, Caplan, R., Malhotra, Savita, Ledda, Maria Giuseppina, Fratta, Al, Mannino, S., Corona, Simona, Zuddas, A., Olalla, Macarena Marin, Garcia, Ruth, Ramirez, Bernardo Perez, Campion, Ross, Hindley, Peter, Gupta, Nitin, Bhattacharaya, Anish, Kapoor, Mehak, van de Willge, G., Klemm, Silke, Smesny, S., Stockebrand, M., Grunwald, S., Juffer, Femmie, van Ijzendoorn, Marinus H., Bakermans-Kranenburg, Marian J., Ziegenhain, Ute, Derksen, B., Dreisörner, R., Gutschner, Daniel, Maldonado-Duran, Martin, Ferndndez-Criado, Manuel, Heidenreich, Felicia, Moro, Marie Rose, Millhuff, Charles, Pope, Kirby, Theisen, Frank, Himmerich, Hubertus, Kraus, T., Schuld, A., Pollmächter, T., Apter, Alan, Gothelf, D., Brand-Gothelf, A., Ratzoni, Gidi, Kikinzon, L., Weizman, A., Bloch, Yuval, Haberhausen, Michael, Müller, Daniel, Fayyad, John, Filho, Altino Bessa Marques, de Menezes, Adolfo Bezerra, Campo, John, Shafer, Sheree, Strohm, Jennifer, Lucas, Amanda, Shaeffer, David, Altman, Harold, Gelachek, Christine, Motomura, Naoyasu, Takino, Yozo, Iwakiri, Masahiro, Pössel, Patrick, Seemann, Simone, Hautzinger, Martin, Mutale, Theodore, Haase, Christian, Abidi, Majid Ali, Raheem, Shehla, Faw, Leyla, Hogue, Aaron, Liddle, Howard, Catthoor, Kirsten, Hutsebaut, Joost, Jasinski, Donald, Faries, Douglas, Moore, Rodney, Streeck-Fischer, Annette, Sannwald, Renate, Barth, Gottfried Maria, Schwarz, Christoph, Staigle, Monika, Pham, Manh-Hiep, Balanzin, Dario, Materi, Joelle, Eresund, Pia, Mokhovikov, Alexander, Stankovic, Sandra, Munir, Kerim, Erol, Nese, Çetin, Füsun Çuhadarodlu, Hassiotis, Angela, Flament, Martine, Scholz, Michael, Rix, Maud, Nestler, Franziska, Selisko, Annegret, Godart, Nathalie, Perdereau, Fabienne, Rein, Zoé, Curt, Florence, Akister, Jane, Lee, Pei-Chin Peggy, Tsai, Sho-Man Susan, Ho, Lai-Shiun, Wu, Su-Chun, Miermont, Jacques, Swenson, Joel, Teherani, Mardjane, Falissard, Bruno, Cottraux, Jean, Plück, Julia, Oades, Robert, Simons-Sprong, Mirjam, Schothorst, P. F., Swaab-Barneveld, J. T., Juran, Stephanie, Weisbrod, Matthias, Chen, Eric, Röpcke, Bernd, Popovic-Deusic, Smiljka, Poustka, Luise, Wild-Wall, Nele, Papousek, Mechthilde, Keren, Mirelle, Feldman, Ruth, Maestro, S., Chilosi, A., Pecini, C., Pfanner, L., Greenhill, Laurence, Jahnsen, K., den Berg, L. T. W. Jong-van, Zito, J. M., Posner, Kelly, Skrobala, Anne, Goldberg, Pablo, Kotler, Lisa, Findling, Robert, Bussing, Regina, Sayal, Kapil, Mitchell, Geoffrey, Huss, Michael, Högl, Barbara, Grimmlinger, Renate, Käppler, Karl Christoph, Teodoro, Maycoln M. L., Oswald, Sylvia Hiromi, Dagnoni, Janine M., Pinheiro, M. I., Heleno, C. T., Rothe-Neves, R., Haase, V. G., Prette, A. Del, Lambertucci, Marimilia Rodrigues, Rodrigues, J. L., Freitas, P. M., Lourenco, C. A. P., Carvalho, H. C. W., Baumeister, J., Weisenhorn, M., Stadelmann, S., Oswald, S. H., Ruder, H., Ruggerini, Ciro, Vicini, Stefania, Pupulin, Enrico, Guidi, Antonio, Puura, Kaija, Mäntymaa, Mirjami, von Klitzing, Kai, Rosvald, Orna, Kröber, Hans-Ludwig, Stöver, A., Proske, R., Semmelbeck, Rainer, Walther, Marc, Schmelzle, Matthias, Egli-Alge, Monika, Beckett, Richard, Gerhold, Constanze, Turkmen-Barta, Lieselotte, Chiland, Colette, Meyer-Bahlburg, Heino, Ceglie, Domenico Di, Lehmkuhl, Ulrike, Uccellini, Orlando, Bertolini, Mario, Neri, Francesca, Albanese, Delia, Bertola, Raffaella, Snoek, Maartje, Kas, Martien, Schulze, Ulrike Margarete Elisabeth, Calame, Silke, Keller, Ferdinand, Santel, Stephanie, Krauel, Kerstin, Rotte, Michael, Münte, Thomas F., van Elburg, Annemarie, Poustka, Fritz, Bölte, Sven, Feineis-Matthews, Sabine, Boite, Sven, Hubl, D., Prvulovic, D., Dierks, T., Klauck, Sabine, Moilanen, Irma, Mattila, M., Laurila, J., Jussila, K., Pyper, A., Linna, S. L., Ebeling, Hanna, Pauls, D., Korpilahti, Pirjo, Loukusa, Soile, Jansson-Verkasalo, Eira, Hebebrand, Johannes, Herpertz-Dahlmann, Beate, Hinney, Anke, Wermter, Anne-Kathrin, Friedel, Susann, Geller, Frank, Schafer, Helmut, Fernandez-Aranda, Fernando, Holliday, Joanna, Holtkamp, Kristian, Mika, C., Heer, M., Uher, Rudolf, Barbarich, Nicole, Henry, Shannan E., Bailer, Ursula, Frank, Guido, Kaye, Walter H., Wentz, Elisabet, Lacey, J. Hubert, Waller, Glenn, Rastam, Maria, Turk, Jeremy, Gillberg, Christopher, Verhulst, Frank C., Zwaanswijk, Marieke, Verhaak, Peter, Bensing, Jozien, van der Ende, Jan, Verhulst, Frank, Sourander, Andre, Santalahti, Paivi, Ford, Tamsin, Goodman, Robert, Meltzer, Howard, Seiffge-Krenke, Inge, Fritsch, Richard, Cutler, Marika, Anthony, E. James, Rydelius, Per-Anders, Castell, Rolf, Pejovic-Milovancevic, Milica, Pavlovic, Miroslav, Kalman, Noa, Linder, Muli, Luria, Ido, Levkovitz, Yechiel, Yamazaki, Kosuke, da Silva, Pedro Caldeira, Santos, Grata, Martins, Filipa, Chiu, Yen-Nan, Tsai, Wen-Jer, Gau, Shur-Fen, Tseng, Chang-Chang, Su, Shu-Chen, Croonenberghs, Jan, Brouw, Lucas, Wauters, Annick, Bruning, Nicole, Manjaly, Zina, Fink, Gereon, Aleksic, Olivera, Rudic, Nenad, Jansen, Lucres, Wied, Christine C. Gispen-De, Lahuis, Bertine, Swaab, Hanna, Pietersen, Jolijn, Gevers, Carolien, Kamp-Becker, Inge, Germerott, Isabell, Howlin, Patricia, Gaudière, Forresi, Barbara, Lepri, G., Laval, Soumaila, Wiefel, Andreas, Biringen, Z., Titze, Karl, Lenz, K., Seither, C., Witte, B., Dunitz-Scheer, Marguerite, Wilken, Markus, Krasnovsky, Alexandra, Scheer, Peter, Cordeiro, Maria, Muratori, Filippo, Felloni, B., Cesari, A., Helmig, Linda, Fonagy, Peter, Moody, Chris, Fultz, Jim, Glanzmann, René, Lutz-Latil, Nathalie, van Wyl, Agnes, Puras, Dainius, Hervds, Amaia, Tsiantis, John, Dragonas, T., Davis, H., Ispanovic, V., Paradisiotou, A., Shanini, Mimoza, Jones, Lynne, Uka, A., Rrustemi, A., von Knorring, Anne-Liis, Deboutte, Dirk, Dorhmi, Souraya, Agoub, Mohamed, Moussaoui, Driss, Battas, Omar, Halvorsen, Inger, Andersen, Anne, Heyerdahl, Sonja, Baillot, Denise, La Roche, Michele, Furino, Claudia, Buchholtz, Annick, Goldfield, Gary, Henderson, Katherine, Hagenah, Ulrich, Blume, Varinja, Flacke-Redanz, Marlene, Dahlmann, Beate Herpertz, Sallas, Angelique A., Adam, Hubertus, Ephraime, Boia, Jr., Mozambique, Goci-Uka, Aferdita, Schlüter-Müller, Susanne, Bawa, Umesh, Khalik, Fakhri, Forouher, Nima, Sadamatsu, Miyuki, Nanba, Kato, Nobumasa, Kasai, Kiyoto, Nanba, Eiji, Schmidt, Martin H., Esser, Günter, van Engeland, Herman, Willemsen-Swinkels, Sophie, Dietz, Claudine, Beernink, Anne Claire, Vidojevic, Oliver, Milacic, Ivona, Strous, Rael, Hegesh, Roni, Kertzman, Simion, Ben-Nahum, Z., Kotler, Moshe, van Daalen, Emma, Zeegers, Mijke, Pol, Hilleke Hulshoff, Williams, Charles, Sank, Jessica, Paulk, Martha, Schwarz, George, Wharton, Paul, Raleva, Marija, Paketchieva, Kamka, Filipovska, Angelina, Nix, Carole Müller, Guex, Margarita Forcada, Daigham, Abdel-Mohsen, Indredavik, Marit S., Vik, Torstein, Kulseng, Siri, Brubakk, Ann-Mari, Cuddy, Marion, Riley, Katharine, Vollmer, Brigitte, Wyatt, John, Murray, Robin, Soininen, Mika, Paavonen, E. Juulia, Fjällberg, Mika, Salmi, Juha, Fredrik, Almgvist, Aronen, Eeva T., Reis, Olaf, Bohne, Stephanie P., Kraenz, Susanne, Ahn, Dong-Hyun, Kim, Tae-Ho, Choi, Jun-Ho, Kim, Yun-Young, Begovac, Ivan, Skocic, Milena, Rudan, Vlasta, Filipovic, Oleg, Wolanczyk, Tomasz, Brynska, Anita, Wojtowicz, Stanislaw, Celia, Salvador, Aerts, Cisca, Cleve, Elisabeth, Hartmann, Hellmut, Kühle, Hans-Jürgen, Heidorn, Fridjof, Zeyer, Solveigh, Fuentes, Joaquin, Martin, Andrés, Sukhodolsky, Denis G., Kaltiala-Heino, Riittakerttu, Rimpelä, Matti, Andershed, Henrik, O’Donnell, Deborah, Pearce, Michelle, Burgin, Dieter, Becker, Andreas, Hagenberg, Nicola, Berking, Matthias, Roessner, Veit, Hanssen-Bauer, Ketil, Aalen, Odd, Junglas, Jürgen, Huh, Yoon-Seok, Kim, Yun Young, Oh, Kyung-Ja, Wang, Kai, Tarren-Sweeney, Michael, Leiblum, D. M., Kühl, Renate, Nötzel, Cornelia, Pfeiffer, Ernst, Lenz, Klaus, Rosling, Agneta, Poller, Marianne, Cross, Donna, Klabin, Simone, Kaplan, Diana, Mickel, Lars, Lehmkuhl, Gerd, Möckel, Regina, Leor, Shani, Frisch, Leor, Frisch, Amos, Weizman, Abraham, Zanozin, Andrey, Jamart, Sylvie, Hayez, Jean-Yves, Leor, Agnes, Ahle, Maria Elisabeth, Amitay, Galit Ben, Kosov, Irene, Reiss, Ahuva, Tamar, Moses, Smedje, Hans, Allik, Hiie, Steyaert, Jean, Castermans, Dries, Creemers, John, Kaczynska-Haladyj, Koenraad Devriendt Marta, Ballabriga, Maria Claustre Jané, Judez, Joaquima, Pelaez, Empar, Sole, Pilar, Rodriguez, Lidia, Palmen, Saskia, Kemner, Chantal, Schnack, Hugo, Kahn, Rene, Fabrizi, Anna, Gabriel, Levi, Mercadante, Marcos, Ramos, Sergiode Paula, Rosario-Campos, Maria Concecao, Rutter, Michael, Collishaw, Stephan, Maughan, Barbara, Pickles, Andrew, Messer, Julie, Caspi, Avshalom, Moffitt, Terrie, Kreppner, Jana, Borge, Anne Inger H., Luthar, Suniya, Hamarman, Stephanie, Ulger, C., Fossella, J., Brimacombe, M., Dermody, J., Stein, Mark, Waldman, L. D., Sarampote, C., Robb, A., Cook, E. H., Kirley, Aiveen, Lowe, N., Hawi, Z., Mullins, C., Daly, G., Waldman, I., McCarro, M., O’Donell, van der Meulen, Emma, Bakker, S. C., Pauls, D. L., Sinke, R. J., Polanczyk, Guilherme, Zeni, C., Genro, J. P., Roman, Tatiana, Hutz, Mara, Schaff, Christa, Haemmerle, Patrick, Sontag, Harald, Vetro, Agnes, Gadoros, Julia, Roosen-Runge, Gotthard, Hattab, Jocelyn, Hummel, Peter, Braun-Lewensohn, Orna, Schechter, Daniel, Zeanah, Charles, Myers, Michael, Liebowitz, Michael, Davies, Mark, Soong, Wei-Tsuen, James, Deborah, Sofroniou, Nick, Gegelashvili, Marine, Parikh, Umesh, Kane, John M., Malhotra, Anil K., Shah, Manoj, Pleak, Richard R., Hizami, Ronen, Michelson, David, Danckaerts, Marina, Zuddas, Alessandro, Zhang, Shuyu, Hazell, Philip, Zeiner, P., Johnson, M., Häßler, Frank, Suyash, Prasad, Sonuga-Barke, Edmund, Poole, Lynne, Mares, Sarah, Jureidini, Jon, Steel, Zachary, Newman, Louise, Lucas, Torsten, Paulus, Stephanie, Aßhauer, Martin, Miller, Birgit, Björn, Gunilla Jarkman, Bodén, Christina, Gustafsson, Per, Ivkic, Viola Povse, Tenjovic, Lazar, Jelena, Radosavljev, Deusic, Smiljka Popovic, Graham, Philip, Klasen, Henrikje, Tan, Jacinta, Hope, Tony, Stewart, Anne, Fitzpatrick, Raymond, Kölch, Michael, Diaz-Caneja, Angeles, Johnson, Sonia, Dippold, Ines, Keller, Katja Wiethoffi Ferdinand, Bailey, Sue, Whittle, Nathan, Hennighausen, Klaus, Kohls, Gregor, Maas, Verena, Rinker, Tanja, Zachau, Swantje, Christmann, Gabriele, Jaremkiewicz, Anna, Schecker, Michael, von Suchodoletz, Waldemar, Uwer, Ruth, Albrecht, Ronald, Glass, Lisa, Csépe, Valéria, Honbology, Ferenc, Rago, Anett, Mészdros, Eva, Schwartz, Richard G., Shafer, Valerie L., Green, Jonathan, Jacobs, C., Kroll, L., Briskman, J., Dunn, G., Beecham, J., Tobias, B., Baird, L., Ogden, Terje, Fitzgerald, Michael, Bellgrove, Mark, Gill, Michael, Robertson, Ian H., McArdle, Paul, Burke, Amanda, Hong, K. Michael, Hoven, Christina, Wasserman, Danuta, Braun, Katharina, Bock, Jórg, Helmecke, Carina, Gruß, Michael, Poeggel, Gerd, Marsden, Charles, Muchimapura, S., Pardon, M.-C., Bianchi, M., Feldon, Joram, Rüedi-Bettschen, Daniela, Dettling, Andrea C., Pryce, Christopher R., Clement, Hans-Willi, Sommer, O., Pschibul, A., Rombach, C., Gerlach, M., Mehler-Wex, Claudia, Zeiske, S., Grünblatt, E., Gille, G., Rausch, D., Gerlach, Manfred, El-Din, Amira Seif, Kadri, Nadia, Andaloussi, Houda Hjiej, Chihabeddine, Khadija, Almaqrami, Mohammed, von Gontard, Alexander, Okuno, M., Quaschner, Kurt, Bilenberg, Niels, Obel, Carsten, Henriksen, Tine Brink, Hedegaard, Morten, Secher, Niels Jurgen, Olsen, Jorn, Fonseca, Antonio, Koch, Isabelle Nathalie, Bite, Ieva, Cohen, Phyllis, Russell, Katrin, Broyden, Nichaela, Lancaster, Gillian, Eichhorn, Christina, Tiedtke, Karola, Feldman, Ronald, Warnke, Andreas, Scheuerpflug, Peter, Vetter, V., Bartling, Jürgen, Konrad, Kerstin, Neufang, Susanne, Hanisch, Charlotte, Fink, Gereon R., Durston, Sarah, Davidson, Matthew C., Tottenham, Nim, Spicer, Julie, Galvan, Adriana, Horvitz, John, Fossella, John A., Watts, Richard, Casey, B. J., Brandeis, Daniel, Fallgatter, Andreas J., Ehlis, Ann-Christine, Seifert, Jürgen, Strik, W. K., Zillessen, K. E., Herrmann, Martin J., Schulte-Körne, Gerd, Lyytinen, Heikki, Guttorm, Tomi, Poikkeus, Anna-Maija, Eklund, Kenneth M., Lyytinen, Paula, Torppa, Minna, Laakso, M.-L., Leskinen, E., Tolvanen, A., Paracchini, Silvia, Schumacher, J., König, I. R., Libertus, Claudia, Griesemann, Heide, Kleensang, A., Ziegler, A., Propping, P., Näthen, M., Wolmer, Leo, Zagout, Iyad, Galili-Weisstub, Esti, Fisch, Gene, Swillen, Ann, Vogels, Annick, Freitag, Christine, Bouville, Jean-Francois, Atlanti-Duault, Laetitia, Baubet, Thierry, Osrow, Robyn, Leplomb, Marie-Madeleine, Marchandy, Yves, Bennabi, Malika, Halpern, Ricardo, Monteiro, Odon, Durkin, Abbey-Robin, Haapanen, Rudy, Bauer, Susanne, Friedrich, Max, Stadler, Christina, Sterzer, Philipp, Kleinschmidt, Andreas, Nowraty, Irene, Müller, W. E., Knölker, Ulrich, Schmid, Gabriele, Berndt, Swantje, Behn, B., Puls, Jan Hendrik, Stevens, Luc, Jungmann, Joachim, Juretic, Zoran, Ercegovic, Nela, Schepker, Renate, Çuhadaroglu-Çetin, Füsun, Herhaus, G., Melfsen, S., Cheng, Daomeng, Harder, Donald, Laws, Harry, Nakane, Yoshibumi, Takeshita, Kenzo, Naruse, Hiroshi, Zhu, Yan, Liu, Jun, Du, Yasong, Sikorski, John, Hamerlynck, Sannie, Hart, Lisettet, Nauta-Janssen, Lucres, Chitsabesan, Prathiba, Nguyen, Hien, Simeon, Jovan, Cuzner, Cathy, Schachter, Howard, Martins, Ana Soledade, Kieling, Chirstian, Comassetto, Julia, Goncalves, Renata, Oswald, Silvia, Buchmann, Johannes, Kirschner, J., Garvey, M., Moll, Gunther, Heinrich, Hartmut, Malhotra, Sameer, Poulakis, Zeffie, Menahem, Sam, Sauer, Karin, Samia, Tilouch, Rimeh, Hannachi, Sonia, Missaoui, Allodi, Mara Westling, Biscaldi, Monica, Wagner, Bettina, Uchida, Chiyoko, Jozefiak, Thomas, Penge, Roberta, Biaggini, Valentina Ivancich, Fischbein, Siv, Joukamaa, Matti, Taanila, Anja, Veijola, Juha, Karvonen, Juha T., Miettunen, Jouko, Llaberia, Edelmira Domenech, Domenech, Teresa Corbella, Ballabriga, Maria Claustre Jane, Sanz, Josepa Canals, Esparo, Griselda, Sola, Sergi Ballespi, Liu, Xuejun, Kano, Yukiko, Ohta, Masataka, Nagai, Yoko, Arai, Takashi, Linyan, Su, Bridge, Jeff, Birmaher, Boris, Di Lorenzo, Carlo, Iyengar, Satish, Brent, David, Blanz, Bernhard, Weninger, Laura, Libal, Gerhard, Skrabal, Anna, Bowden, Michael, Cooper, Howard, Simonsen, Inger, Bechstrom, Carl, Medby, Mette, Erkolahti, Ritva, Klosinski, Gunther, Oba, Mihoko, Murase, Satomi, Murakami, Takashi, Takai, Jiro, Kaneko, Hitoshi, Honjo, Shuji, Rickards, Katrina, Weber, Annhild, Karle, Michael, Lazartigues, Alain, Planche, Pascale, Lemonnier, Eric, Pavuluri, Mani, Schenkel, Lindsay, Shaw, Ryan, Sweeny, John, Rigon, Giancarlo, Costa, Stefano, Mancaruso, Alessandra, Mansi, Roberta, Poggioli, Daniele Giovanni, Chiodo, Simona, Radobuljac, Maja, Groleger, Urban, Ovsenik, Nada, Tomori, Martina, Haas, Barbara, Denoix, Susanne, Kimmig, Franz, Weinhardt, Marc, Schmitz, Günter, Filschke, Berit, Fliegauf, Conny, Kim, Ji-Hae, Krischer, Maya, Stone, Michael H., Sevecke, Kathrin, Doepfner, Manfred, König, Cornelia, Grasmann, Dörte, Schlander, Michael, Ralston, Stephen, Pereira, R. Rodrigues, Brussel, W., Vlasveld, L., Tuynman-Qua, H. G., Lorenzo, M. J., Tauscher-Wisniewski, R., Palazzi, Stefano, Guaia, Ettore, Kolakowski, Artur, Pisula, Agnieszka, Wilens, Timothy, Banaschewski, Tobias, Uebel, Henrik, Albrecht, Björn, Robatzek, Monika, Migliaccio-Walle, Kristen, Caro, Jaime, Allen, Albert J., Sangal, R. Bart, Owens, Judith, Kelsey, Douglas, Sutton, Virginia, Schuh, Kory, Bahadir, Aliye Tugba, Yaman, Zeynep, Arman, Ayse Rodopman, Kuscu, Kemal, Yazgan, Yanki, Berkem, Meral, Feldman, Peter, Denai, Milton, Simpson, Alexander, Kratochvil, Christopher, Newcorn, Jeffrey, Biederman, Joseph, Gelowitz, Douglas, Thomason, Christine, Gao, Haitao, Bijttebier, Patricia, Decoene, Steff, Niklaus, Pia, Duits, Nils, Auer, Ulrich, Schnoor, Kathleen, Schläfke, Detlef, Çetin, Füsun Çuhadaroälu, Harper, Gordon, Hamdan, Sami, El-Haib, Muhammed, Canat, Saynur, Halfon, Olivier, Bolognini, Monique, Plancherel, B., Phan, Olivier, Corcos, Maurice, Cardinaux, Jean-René, Magistretti, Pierre J., Pierrehumbert, Blaise, Koskinen, Minna, Engqvist, Ulf, Allin, Matthew, Rifkin, Larry, Lancaster, Sandra, Borghini, Ayala, Jaugey, Laure, Forcada-Guex, Margarita, Jaunin, Lyne, Müller-Nix, Carole, Ansermet, François, Simoes, Mariada Conceicao Taborda, Lima, Luiza Nobre, Dias, Mariada Luz Vale, Siefen, Rainer Georg, Como, Ariel, Alikaj, Valbona, Tomori, Sonila, Capozzi, Flavia, Romano, Angela, Roello, Mara, Piperno, Francesca, Mann, Mali A., Stösser, Dieter, Barth, Gottfried, Pimenov, Alina, Schwab, Jenny, Bingöl, Hülya, Barbe, Rémy, Elkshishy, Heba, Jovanovic, Ana, Lakic, Aneta, Milovanovic, Vesna, Vukasinovic, Milorad, Bridge, Jeffrey, Kolko, David, Brent, David A., Gilson, Kathryn, Montague, Roslyn, Shochet, Ian, Marques, Cristina Maria Ribeiro, Cepeda, Teresa, Ligges, Carolin, Ligges, Marc, Huonker, Ralph, Leppänen, Paavo, Guttorm, Torni K., Hämäläinen, Jarmo, Puolakanaho, Anne, Plume, Ellen, König, Inke R., Deimel, Wolfgang, Nöthen, Markus M., Propping, Peter, Kleensang, André, Müller-Myhsok, Bertram, Ziegler, Andreas, Hong, Sung-Do David, Gao, Xueping, Li, Xuerong, Lee, Soyoung Irene, Kim, Eui-Jung, Cho, In-Hee, Kim, Ji-Hoon, Park, Se-Hyun, Choi, J-Wook, Heger, Steffen, Schreiner, Andreas, Rettig, Klaus, Medori, Rossella, Gustafsson, Peik, Hansson, Kjell, Eidevall, Lena, Thernlund, Gunilla, Heiser, Philip, Dempfle, A., Smidt, Judith, Grabarkiewicz, Justyna, Kiefl, Hans, Hemminger, U., Saar, K., Swanson, James, Volkov, Nora D., Gupta, S., Williams, L., Agler, D., Wasdell, M., Wigal, S., Martins, Silvia, Tramontina, Silza, Eizirik, Mariana, Vitiello, Benedetto, Clevenger, Walter, Faraone, Stephen, McGough, James, McCracken, James, Rohde, Luis Augusto, Greenhill, Larry, Leary, Michael, Larsson, Bo, Gunning, W. Boudewijn, Villat, Jean-Marie, O’Connell, Redmond, Bellgrove, Mark A., Dockree, Paul, Traube, Raymond, Braunschweig, Mary, Chabanier, Jacques, De Leo, Germana, Ibanez, Margerita, Mikolajaks, Olivette, Ropstad, Ida, Young, J. Gerald, Aiello, Rachele, Porcari, Viviana, Salatiello, Maria Patrizia, Lo Bue, Anna, Dell’Oglio, Valentina, Cardella, Rosaria, Chifari, Sabrina, Undheim, Anne Mari, Su, Linyan, Luo, Xuerong, Barton, Joanne, Baying, Lioba, Rellum, Thomas, Duezel, Emrah, Hinrichs, Hermann, Bartel, Christoph, Linde, Iris, Friederichs, E., Bangs, Mark, Remschmidt, Helmut, Doreleijers, Theodore, Rebernig, Elisabeth, Camerini, Giovanni Battista, Otero, Soraya, Rivas, Ana, Pombo, Guadalupe, Yeghiyan, Maruke, Kachatur, Gasparyan, Danileyan, Arman, Ivarsson, Tord, Valderhaug, Robert, Walitza, Susanne, Wewetzer, Christoph, Barth, Nikolaus, Hahn, F., Asbahr, Fernando, Castillo, Ana Regina, Ito, Ligia, Latorre, Mariado Rosario, Moreira, Michelle, Lotufo-Neto, Francisco, Symann, Sophie, Charlier, Dominique, Plattner, Belinda, Schallauer, Astrid Elisabeth, Mohler, Beat, Staub, P., Müller, Carsten, Oelkers-Ax, Rieke, Fischer, Jochen, Hermanns, Uta, Nickel, Anne, Bolay, Hans Volker, Cherro-Aguerre, Miguel, Sorensen, Merete Juul, Nissen, Judith Becker, Mors, Ole, Thomsen, Per Hove, Sund, Anne Mari, Drugli, May Britt, Wichstrom, Lars, Schwannauer, Matthias, Taylor, Emily, Wrate, Rob, Martin, Matthias, Larsson, Jan-Olov, Larsson, Henrik, Lichtenstein, Paul, Ludolph, Andrea G., Mottaghy, Felix, Kraemer, Susanne, Claus, Dieter, Krause, Bernhard, Fegert, Jbrg M., Hurtig, Tuula, Malakhova, Anna, Maniadaki, Katerina, Kakouros, Efthymios, Jensen, Peter, Garcia, Joe Albert, Glied, Sherry, Crowe, Maura, Foster, E. Michael, Golse, Bernard, Junghanß, Jenny, Salin, Aino-Maija, Rytölä, Päivi, Hiltunen, Pauliina, Remschmidt, Helmut, editor, and Belfer, Myron L., editor

Published
2004
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6. 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 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, 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 M.J., 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 A.M., 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, 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 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, 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., van den Heuvel, Leigh Luella, 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 Mc D., 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., Nievergelt, Caroline M., 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, 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 M.J., 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 A.M., 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, 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 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, 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., van den Heuvel, Leigh Luella, 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 Mc D., 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.

Abstract

Background: 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 (GWASs). Methods: A 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. Results: GWASs 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. Conclusions: Through 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

9. ROLE OF THE ALLELIC VARIATION IN THE 5-HYDROXYTRYPTAMINE RECEPTOR 1A (HTR1A) AND THE TRYPTOPHAN HYDROXYLASE 2 (TPH2) GENES IN THE DEVELOPMENT OF PTSD

Author

Afërdita Goçi Uka, Ferid Agani, Afrim Blyta, Blerina Hoxha, Shpend Haxhibeqiri, Valdete Haxhibeqiri, Emina Sabic Dzananovic, Sabina Kucukalic, Alma Bravo Mehmedbasic, Abdulah Kucukalic, Alma Dzubur-Kulenovic, Elma Feric Bojic, Damir Marjanovic, Nermina Kravic, Esmina Avdibegovic, Mirnesa Muminovic Umihanic, Nenad Jaksic, Ana Cima Franc, Dusko Rudan, Miro Jakovljevic, Romana Babic, Marko Pavlovic, Dragan Babic, Branka Aukst Margetic, Nada Bozina, Osman Sinanovic, Christiane Ziegler, Bodo Warrings, Katharina Domschke, Jürgen Deckert, Christiane Wolf, Afërdita Goçi Uka, Ferid Agani, Afrim Blyta, Blerina Hoxha, Shpend Haxhibeqiri, Valdete Haxhibeqiri, Emina Sabic Dzananovic, Sabina Kucukalic, Alma Bravo Mehmedbasic, Abdulah Kucukalic, Alma Dzubur-Kulenovic, Elma Feric Bojic, Damir Marjanovic, Nermina Kravic, Esmina Avdibegovic, Mirnesa Muminovic Umihanic, Nenad Jaksic, Ana Cima Franc, Dusko Rudan, Miro Jakovljevic, Romana Babic, Marko Pavlovic, Dragan Babic, Branka Aukst Margetic, Nada Bozina, Osman Sinanovic, Christiane Ziegler, Bodo Warrings, Katharina Domschke, Jürgen Deckert, and Christiane Wolf

Abstract

Background: Post-traumatic stress disorder (PTSD) is a stress related disorder which can occur in an individual after exposure to a traumatic event. It most commonly co-occurs with depression. The two disorders share not only overlapping symptoms, but also genetic diathesis. The aim of this study was to investigate the potential role of single nucleotide polymorphisms (SNPs) of the two serotonergic candidate genes 5-hydroxytryptamine receptor 1A (HTR1A) and tryptophan hydroxylase 2 (TPH2) in the pathogenesis of PTSD and comorbid psychopathology. Subjects and methods: 719 (487 males, 232 females) participants who had experienced war-related trauma between 1991 and 1999 in Bosnia and Herzegovina, Kosovo and Croatia were included in the study. The Sociodemographic questionnaire, Mini International Neuropsychiatric Interview (M.I.N.I.), Clinician Administered PTSD Scale (CAPS) and Brief Symptom Inventory (BSI) were used to collect clinical data. The SNPs rs6295 (HTR1A), rs11178997 and rs1386494 (TPH2) were investigated for their association with PTSD and comorbid psychopathology. Results: A nominal significant association was found between the BSI total score in Lifetime PTSD with the SNP rs6295 of the HTR1A gene. The best result was seen in the dominant model (P=0.018), with the minor allele (C) being the risk allele. Several BSI subscores were also associated with the minor (C) allele in Lifetime PTSD. No association was found for the TPH2 SNPs rs11178997 and rs1386494 in relation to PTSD or comorbid psychopathology. Conclusions: Our findings suggest that rs6295 in the HTR1A gene may contribute to the psychopathology of PTSD.

Published
2019

10. THE ROLE OF TAQI DRD2 (RS1800497) AND DRD4 VNTR POLYMORPHISMS IN POSTTRAUMATIC STRESS DISORDER (PTSD)

Author

Blerina Hoxha, Afërdita Goçi Uka, Ferid Agani, Shpend Haxhibeqiri, Valdete Haxhibeqiri, Emina Sabic Dzananovic, Sabina Kucukalic, Alma Bravo Mehmedbasic, Abdulah Kucukalic, Alma Dzubur Kulenovic, Elma Feric Bojic, Damir Marjanovic, Nermina Kravic, Esmina Avdibegovic, Mirnesa Muminovic Umihanić, Nenad Jaksic, Ana Cima Franc, Dusko Rudan, Miro Jakovljevic, Romana Babic, Marko Pavlovic, Dragan Babic, Branka Aukst Margetic, Nada Bozina, Osman Sinanovic, Christiane Ziegler, Bodo Warrings, Katharina Domschke, Jürgen Deckert, Christiane Wolf, Gentian Vyshka, Blerina Hoxha, Afërdita Goçi Uka, Ferid Agani, Shpend Haxhibeqiri, Valdete Haxhibeqiri, Emina Sabic Dzananovic, Sabina Kucukalic, Alma Bravo Mehmedbasic, Abdulah Kucukalic, Alma Dzubur Kulenovic, Elma Feric Bojic, Damir Marjanovic, Nermina Kravic, Esmina Avdibegovic, Mirnesa Muminovic Umihanić, Nenad Jaksic, Ana Cima Franc, Dusko Rudan, Miro Jakovljevic, Romana Babic, Marko Pavlovic, Dragan Babic, Branka Aukst Margetic, Nada Bozina, Osman Sinanovic, Christiane Ziegler, Bodo Warrings, Katharina Domschke, Jürgen Deckert, Christiane Wolf, and Gentian Vyshka

Abstract

Background: Posttraumatic stress disorder (PTSD) is a complex stress related disorder, that follows a severe traumatic experience, characterized with an intense sense of terror, fear, and helplessness. The aim of this study is to identify associations of genetic variations within candidate genes DRD2 and DRD4 with various PTSD related phenotypes. PTSD lifetime and PTSD current subjects were analyzed separately, each of them were analyzed in a Case/Control design, as well as regarding BSI and CAPS within cases only. Subjects and methods: 719 (487 male, 232 female) participants who had experienced war-related trauma between 1991 and 1999 in Bosnia and Hercegovina, Kosovo and Croatia were included in the study. Sociodemographic questionnaire, Clinician Administered PTSD Scale (CAPS) and the Brief Symptom Inventory (BSI) were used to collect clinical data. Results: The DRD2 rs1800497 variant and a variable number tandem repeat (VNTR) located in exon three of DRD4 were investigated for association with PTSD. In case control analyses we did not identify any significant associations. Within the PTSD current patients, we identified an association of DRD2 rs1800497 with BSI in the genotypic and the recessive model with the T allele as the risk allele. Conclusion: Our findings suggest that rs1800497 of DRD2 gene is involved in pathogenesis of PTSD.

Published
2019

12. THE ROLE OF TAQI DRD2 (RS1800497) AND DRD4 VNTR POLYMORPHISMS IN POSTTRAUMATIC STRESS DISORDER (PTSD).

Author

Hoxha, Blerina, Uka, Afërdita Goçi, Agani, Ferid, Haxhibeqiri, Shpend, Haxhibeqiri, Valdete, Dzananovic, Emina Sabic, Kucukalic, Sabina, Mehmedbasic, Alma Bravo, Kucukalic, Abdulah, Kulenovic, Alma Dzubur, Bojic, Elma Feric, Marjanovic, Damir, Kravic, Nermina, Avdibegovic, Esmina, Umihanić, Mirnesa Muminovic, Jaksic, Nenad, Franc, Ana Cima, Rudan, Dusko, Jakovljevic, Miro, and Babic, Romana

Published
2019
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13. ROLE OF THE ALLELIC VARIATION IN THE 5-HYDROXYTRYPTAMINE RECEPTOR 1A (HTR1A) AND THE TRYPTOPHAN HYDROXYLASE 2 (TPH2) GENES IN THE DEVELOPMENT OF PTSD.

Author

Uka, Afërdita Goçi, Agani, Ferid, Blyta, Afrim, Hoxha, Blerina, Haxhibeqiri, Shpend, Haxhibeqiri, Valdete, Dzananovic, Emina Sabic, Kucukalic, Sabina, Mehmedbasic, Alma Bravo, Kucukalic, Abdulah, Dzubur-Kulenovic, Alma, Bojic, Elma Feric, Marjanovic, Damir, Kravic, Nermina, Avdibegovic, Esmina, Umihanic, Mirnesa Muminovic, Jaksic, Nenad, Franc, Ana Cima, Rudan, Dusko, and Jakovljevic, Miro

Published
2019
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14. P.3.013 - Hypermethylation of the monoamine oxidase A gene – a new epigenetic marker for posttraumatic stress disorder?

Author

Ziegler, C., Wolf, C., Schiele, M., Bojic, E. Feric, Kucukalic, S., Dzananovic, E. Sabic, Uka, A. Goci, Hoxha, B., Haxhibeqiri, V., Haxhibeqiri, S., Kravic, N., Umihanic, M. Muminovic, Franc, A. Cima, Jaksic, N., Babic, R., Pavlovic, M., Warrings, B., Mehmedbasic, A. Bravo, Rudan, D., Aukst-Margetic, B., Kucukalic, A., Marjanovic, D., Babic, D., Bozina, N., Jakovljevic, M., Sinanovic, O., Avdibegovic, E., Agani, F., Dzubur-Kulenovic, A., Deckert, J., and Domschke, K.

Published
2018
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15. Acne in hirsute women

Author

Lumezi, Besa Gacaferri, primary, Pupovci, Hatixhe Latifi, additional, Berisha, Violeta Lokaj, additional, Goçi, Aferdita Uka, additional, and Gerqari, Antigona, additional

Published
2014
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16. Acne in hirsute women.

Author

Gacaferri Lumezi, Besa, Latifi Pupovci, Hatixhe, Lokaj Berisha, Violeta, Uka Goçi, Aferdita, and Gerqari, Antigona

Subjects
ACNE, HYPERTRICHOSIS, HYPERANDROGENISM, DISEASES in women, RADIOIMMUNOASSAY, ULTRASONIC imaging, LONGITUDINAL method, DIAGNOSIS
Abstract

Introduction: Acne and hirsutism are common manifestations of hyperandrogenism. Aim: To investigate whether or not acne is present in women with hirsutism, associated with different clinical, endocrine and ultrasonographic features. Material and methods: The prospective study included 135 women with hirsutism, aged 14-46 years. We measured the levels of hormones with radioimmunoassay/immunoradiometric assay methods. Results: Acne were present in 63 (47.6%) women with hirsutism. Sixty women had mild forms of acne, including: whiteheads, blackheads, papules and pustules. Only 3 women had moderate to severe acne, including nodules. In a group of women with hirsutism and acne, 6 (9.5%) were obese. In our study we found a high prevalence of androgen excess among hirsute women with acne: total testosterone was increased in 79%, free testosterone in 20.6%, androstenedione in 69.8%, dehydroepiandrosterone sulfate (DHEAS) in 30.1%, 17-OH-progesterone 68.2% and sex hormone-binding globulin (SHBG) was decreased in 33.3% of women. Women with hirsutism and acne have received oral contraceptives for a year, without or in a combination with other medication. Thirty-four (53.9%) women have shown improvement in hirsutism and acne. Conclusions: In this study we found a high prevalence of acne in hirsute women. The prevalence of acne was higher in polycystic ovarian syndrome. Since these women have associated endocrine changes it is important to correct them with hormonal therapy. [ABSTRACT FROM AUTHOR]

Published
2014
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17. How war affected my life and work

Author

Aferdita Goçi-Uka

Subjects
business.industry, Miracle, media_common.quotation_subject, General Engineering, Reviews, General Earth and Planetary Sciences, Medicine, Gender studies, General Medicine, business, nobody, General Environmental Science, media_common
Abstract

After two years of war in Kosova, air strikes began in Prishtina. I lived through three months of extreme anxiety. Every day I expected to get killed by the Serbian police, the paramilitary, a soldier, or even a neighbour. I remember listening to the BBC news, hearing horrific stories of civilians who were killed and buried in mass graves: young people, old people, women, and children. Nobody was safe, not even the politicians who were supposed to have immunity under international law. For the first two weeks I didn't go out at all, not because I felt safe at home, but because I wanted to be near my family in case something happened. I was so anxious during those three months that sometimes I felt as if my head would explode. I was sure that we would all get killed, but hoped that by some miracle my children would survive, or that I would be …

Published
2002

19. Grading of hirsutism based on the Ferriman-Gallwey scoring system in Kosovar women.

Author

Lumezi BG, Berisha VL, Pupovci HL, Goçi A, and Hajrushi AB

Abstract

Introduction: Hirsutism is defined as excess terminal hair that commonly appears in a male pattern in women., Aim: To examine severity and distribution of hirsutism with Ferriman-Gallwey visual scoring system in hirsute women in Kosovo., Material and Methods: This prospective study included 160 women, 135 with hirsutism and 25 as a control group. The Ferriman-Gallwey score is used to evaluate hirsutism. The examiner scored the subjects on a scale of 0-4 for terminal hair growth on eleven different body areas according to the Ferriman-Gallwey scoring system. An Ferriman-Gallwey score of 8 or more was considered diagnostic of hirsutism. A thorough physical examination with specific emphasis on signs of virilization (including frontal baldness, loss of female body contours, increased muscularity, acne, clitoromegaly, and atrophy of breast) was done in all patients., Results: The positive family history of hirsutism was present in 63.7%. In 51.1% of women with hirsutism, the menstrual cycle was regular, 25.2% had oligomenorrhea, 13.3% amenorrhea, 7.4% dysmenorrhea, 1.5% polymenorrhea and 1.5% oligomenorrhea and dysmenorrhea. The age group with the highest scoring comprised women under 20 years and 20-29 years group with an average value of 23.9 and 24.8, respectively. In our study population, 40% of the patients had an Ferriman-Gallwey score of 3 for the upper lip and 47% of patients had an Ferriman-Gallwey score of 3 for the chin., Conclusions: The Ferriman-Gallwey scoring system has a great significance and value to establish the diagnosis of hirsutism and is an acceptable screening method.

Published
2018
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