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2. 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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6. Potential causal association between gut microbiome and posttraumatic stress disorder

Author

Cardiologie, Onderzoeksgroep 2, Brain, MGGZ, Hersenen-Medisch 1, Neurogenetica, Diagnostiek & Vroege Psychose Medisch, He, Qiang, Wang, Wenjing, Xu, Dingkang, Xiong, Yang, Tao, Chuanyuan, You, Chao, Ma, Lu, Ma, Junpeng, Nievergelt, Caroline M., Maihofer, Adam X., Klengel, Torsten, Atkinson, Elizabeth G., Chen, Chia Yen, Choi, Karmel W., Coleman, Jonathan R.I., Dalvie, Shareefa, Duncan, Laramie E., Logue, Mark W., 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, Gelernter, Joel, Geuze, Elbert, Gillespie, Charles, Uka, Aferdita Goci, Gordon, Scott D., Guffanti, Guia, Hammamieh, Rasha, Harnal, Supriya, 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, 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 A.M., Lewis, Catrin E., Linnstaedt, Sarah D., Lori, Adriana, Lugonja, Bozo, Luykx, Jurjen J., Lyons, Michael J., Maples-Keller, Jessica, Marmar, Charles, Martin, Alicia R., Martin, Nicholas G., Maurer, Douglas, Mavissakalian, Matig R., McFarlane, Alexander, McGlinchey, Regina E., McLaughlin, Katie A., McLean, Samuel A., McLeay, Sarah, Mehta, Divya, Milberg, William P., Miller, Mark W., Morey, Rajendra A., Morris, Charles Phillip, Mors, Ole, Mortensen, Preben B., Neale, Benjamin M., 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., Ripke, Stephan, Risbrough, Victoria B., Roberts, Andrea L., Rothbaum, Alex O., Rothbaum, Barbara O., Roy-Byrne, Peter, Ruggiero, Ken, 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., Solovieff, Nadia, Sponheim, Scott R., Stein, Dan J., Sumner, Jennifer A., 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 H., Voisey, Joanne, Wang, Yunpeng, Wang, Zhewu, Werge, Thomas, Williams, Michelle A., Williamson, Douglas E., Winternitz, Sherry, Wolf, Christiane, Wolf, Erika J., Wolff, Jonathan D., Yehuda, Rachel, Young, Keith A., Young, Ross Mc D., Zhao, Hongyu, Zoellner, Lori A., Liberzon, Israel, Ressler, Kerry J., Haas, Magali, Koenen, Karestan C., Cardiologie, Onderzoeksgroep 2, Brain, MGGZ, Hersenen-Medisch 1, Neurogenetica, Diagnostiek & Vroege Psychose Medisch, He, Qiang, Wang, Wenjing, Xu, Dingkang, Xiong, Yang, Tao, Chuanyuan, You, Chao, Ma, Lu, Ma, Junpeng, Nievergelt, Caroline M., Maihofer, Adam X., Klengel, Torsten, Atkinson, Elizabeth G., Chen, Chia Yen, Choi, Karmel W., Coleman, Jonathan R.I., Dalvie, Shareefa, Duncan, Laramie E., Logue, Mark W., 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, Gelernter, Joel, Geuze, Elbert, Gillespie, Charles, Uka, Aferdita Goci, Gordon, Scott D., Guffanti, Guia, Hammamieh, Rasha, Harnal, Supriya, 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, 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 A.M., Lewis, Catrin E., Linnstaedt, Sarah D., Lori, Adriana, Lugonja, Bozo, Luykx, Jurjen J., Lyons, Michael J., Maples-Keller, Jessica, Marmar, Charles, Martin, Alicia R., Martin, Nicholas G., Maurer, Douglas, Mavissakalian, Matig R., McFarlane, Alexander, McGlinchey, Regina E., McLaughlin, Katie A., McLean, Samuel A., McLeay, Sarah, Mehta, Divya, Milberg, William P., Miller, Mark W., Morey, Rajendra A., Morris, Charles Phillip, Mors, Ole, Mortensen, Preben B., Neale, Benjamin M., 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., Ripke, Stephan, Risbrough, Victoria B., Roberts, Andrea L., Rothbaum, Alex O., Rothbaum, Barbara O., Roy-Byrne, Peter, Ruggiero, Ken, 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., Solovieff, Nadia, Sponheim, Scott R., Stein, Dan J., Sumner, Jennifer A., 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 H., Voisey, Joanne, Wang, Yunpeng, Wang, Zhewu, Werge, Thomas, Williams, Michelle A., Williamson, Douglas E., Winternitz, Sherry, Wolf, Christiane, Wolf, Erika J., Wolff, Jonathan D., Yehuda, Rachel, Young, Keith A., Young, Ross Mc D., Zhao, Hongyu, Zoellner, Lori A., Liberzon, Israel, Ressler, Kerry J., Haas, Magali, and Koenen, Karestan C.

Published
2024

7. Potential causal association between gut microbiome and posttraumatic stress disorder

Author

He, Qiang, Wang, Wenjing, Xu, Dingkang, Xiong, Yang, Tao, Chuanyuan, You, Chao, Ma, Lu, Ma, Junpeng, Nievergelt, Caroline M., Maihofer, Adam X., Klengel, Torsten, Atkinson, Elizabeth G., Chen, Chia Yen, Choi, Karmel W., Coleman, Jonathan R.I., Dalvie, Shareefa, Duncan, Laramie E., Logue, Mark W., 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, Gelernter, Joel, Geuze, Elbert, Gillespie, Charles, Uka, Aferdita Goci, Gordon, Scott D., Guffanti, Guia, Hammamieh, Rasha, Harnal, Supriya, 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, 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 A.M., Lewis, Catrin E., Linnstaedt, Sarah D., Lori, Adriana, He, Qiang, Wang, Wenjing, Xu, Dingkang, Xiong, Yang, Tao, Chuanyuan, You, Chao, Ma, Lu, Ma, Junpeng, Nievergelt, Caroline M., Maihofer, Adam X., Klengel, Torsten, Atkinson, Elizabeth G., Chen, Chia Yen, Choi, Karmel W., Coleman, Jonathan R.I., Dalvie, Shareefa, Duncan, Laramie E., Logue, Mark W., 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, Gelernter, Joel, Geuze, Elbert, Gillespie, Charles, Uka, Aferdita Goci, Gordon, Scott D., Guffanti, Guia, Hammamieh, Rasha, Harnal, Supriya, 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, 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 A.M., Lewis, Catrin E., Linnstaedt, Sarah D., and Lori, Adriana

Abstract

Background: The causal effects of gut microbiome and the development of posttraumatic stress disorder (PTSD) are still unknown. This study aimed to clarify their potential causal association using mendelian randomization (MR). Methods: The summary-level statistics for gut microbiome were retrieved from a genome-wide association study (GWAS) of the MiBioGen consortium. As to PTSD, the Freeze 2 datasets were originated from the Psychiatric Genomics Consortium Posttraumatic Stress Disorder Working Group (PGC-PTSD), and the replicated datasets were obtained from FinnGen consortium. Single nucleotide polymorphisms meeting MR assumptions were selected as instrumental variables. The inverse variance weighting (IVW) method was employed as the main approach, supplemented by sensitivity analyses to evaluate potential pleiotropy and heterogeneity and ensure the robustness of the MR results. We also performed reverse MR analyses to explore PTSD’s causal effects on the relative abundances of specific features of the gut microbiome. Results: In Freeze 2 datasets from PGC-PTSD, eight bacterial traits revealed a potential causal association between gut microbiome and PTSD (IVW, all P < 0.05). In addition, Genus.Dorea and genus.Sellimonas were replicated in FinnGen datasets, in which eight bacterial traits revealed a potential causal association between gut microbiome and the occurrence of PTSD. The heterogeneity and pleiotropy analyses further supported the robustness of the IVW findings, providing additional evidence for their reliability. Conclusion: Our study provides the potential causal impact of gut microbiomes on the development of PTSD, shedding new light on the understanding of the dysfunctional gut-brain axis in this disorder. Our findings present novel evidence and call for investigations to confirm the association between their links, as well as to illuminate the underlying mechanisms.

Published
2024

8. 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

10. 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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12. Copy Number Variation in Obsessive-Compulsive Disorder and Tourette Syndrome: A Cross-Disorder Study

Author

McGrath, Lauren M., Yu, Dongmei, Marshall, Christian, Davis, Lea K., Thiruvahindrapuram, Bhooma, Li, Bingbin, Cappi, Carolina, Gerber, Gloria, Wolf, Aaron, Schroeder, Frederick A., Osiecki, Lisa, O'Dushlaine, Colm, Kirby, Andrew, Illmann, Cornelia, Haddad, Stephen, Gallagher, Patience, Fagerness, Jesen A., Barr, Cathy L., Bellodi, Laura, Benarroch, Fortu, Bienvenu, O. Joseph, Black, Donald W., Bloch, Michael H., Bruun, Ruth D., Budman, Cathy L., Camarena, Beatriz, Cath, Danielle C., Cavallini, Maria C., Chouinard, Sylvain, Coric, Vladimir, Cullen, Bernadette, Delorme, Richard, Denys, Damiaan, Derks, Eske M., Dion, Yves, Rosário, Maria C., Eapen, Valsama, Evans, Patrick, Falkai, Peter, Fernandez, Thomas V., Garrido, Helena, Geller, Daniel, Grabe, Hans J., Grados, Marco A., Greenberg, Benjamin D., Gross-Tsur, Varda, Grünblatt, Edna, Heiman, Gary A., Hemmings, Sian M.J., Herrera, Luis D., Hounie, Ana G., Jankovic, Joseph, Kennedy, James L., King, Robert A., Kurlan, Roger, Lanzagorta, Nuria, Leboyer, Marion, Leckman, James F., Lennertz, Leonhard, Lochner, Christine, Lowe, Thomas L., Lyon, Gholson J., Macciardi, Fabio, Maier, Wolfgang, McCracken, James T., McMahon, William, Murphy, Dennis L., Naarden, Allan L., Neale, Benjamin M., Nurmi, Erika, Pakstis, Andrew J., Pato, Michele T., Pato, Carlos N., Piacentini, John, Pittenger, Christopher, Pollak, Yehuda, Reus, Victor I., Richter, Margaret A., Riddle, Mark, Robertson, Mary M., Rosenberg, David, Rouleau, Guy A., Ruhrmann, Stephan, Sampaio, Aline S., Samuels, Jack, Sandor, Paul, Sheppard, Brooke, Singer, Harvey S., Smit, Jan H., Stein, Dan J., Tischfield, Jay A., Vallada, Homero, Veenstra-VanderWeele, Jeremy, Walitza, Susanne, Wang, Ying, Wendland, Jens R., Shugart, Yin Yao, Miguel, Euripedes C., Nicolini, Humberto, Oostra, Ben A., Moessner, Rainald, Wagner, Michael, Ruiz-Linares, Andres, Heutink, Peter, Nestadt, Gerald, Freimer, Nelson, Petryshen, Tracey, Posthuma, Danielle, Jenike, Michael A., Cox, Nancy J., Hanna, Gregory L., Brentani, Helena, Scherer, Stephen W., Arnold, Paul D., Stewart, S. Evelyn, Mathews, Carol A., Knowles, James A., Cook, Edwin H., Pauls, David L., Wang, Kai, and Scharf, Jeremiah M.

Published
2014
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14. 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

15. 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

16. The Microbiome in Posttraumatic Stress Disorder and Trauma-Exposed Controls: An Exploratory Study

Author

Hemmings, Sian M.J., Malan-Müller, Stefanie, van den Heuvel, Leigh L., Demmitt, Brittany A., Stanislawski, Maggie A., Smith, David G., Bohr, Adam D., Stamper, Christopher E., Hyde, Embriette R., Morton, James T., Marotz, Clarisse A., Siebler, Philip H., Braspenning, Maarten, Van Criekinge, Wim, Hoisington, Andrew J., Brenner, Lisa A., Postolache, Teodor T., McQueen, Matthew B., Krauter, Kenneth S., Knight, Rob, Seedat, Soraya, and Lowry, Christopher A.

Published
2017
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18. Enhancing Discovery of Genetic Variants for Posttraumatic Stress Disorder Through Integration of Quantitative Phenotypes and Trauma Exposure Information

Author

Maihofer, Adam X., primary, Choi, Karmel W., additional, Coleman, Jonathan R.I., additional, Daskalakis, Nikolaos P., additional, Denckla, Christy A., additional, Ketema, Elizabeth, additional, Morey, Rajendra A., additional, Polimanti, Renato, 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, Avdibegović, Esmina, additional, Borglum, Anders D., 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, 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, José M., 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, Džubur Kulenović, 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, Gautam, Aarti, additional, Gelaye, Bizu, additional, Gelernter, Joel, additional, Geuze, Elbert, additional, Gillespie, Charles F., additional, Goçi, Aferdita, 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, Jakovljević, 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, Božo, 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 B., 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, 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, 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 A., additional, Wu, Tianying, additional, Ripke, Stephan, additional, Daly, Mark J., additional, Ressler, Kerry J., additional, Koenen, Karestan C., additional, Stein, Murray B., additional, and Nievergelt, Caroline M., additional

Published
2022
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20. Epigenome-wide meta-analysis of PTSD across 10 military and civilian cohorts identifies methylation changes in AHRR

Author

Smith, Alicia K., Ratanatharathorn, Andrew, Maihofer, Adam X., Naviaux, Robert K., Aiello, Allison E., Amstadter, Ananda B., Ashley-Koch, Allison E., Baker, Dewleen G., Beckham, Jean C., Boks, Marco P., Bromet, Evelyn, Dennis, Michelle, Galea, Sandro, Garrett, Melanie E., Geuze, Elbert, Guffanti, Guia, Hauser, Michael A., Katrinli, Seyma, Kilaru, Varun, Kessler, Ronald C., Kimbrel, Nathan A., Koenen, Karestan C., Kuan, Pei Fen, Li, Kefeng, Logue, Mark W., Lori, Adriana, Luft, Benjamin J., Miller, Mark W., Naviaux, Jane C., Nugent, Nicole R., Qin, Xuejun, Ressler, Kerry J., Risbrough, Victoria B., Rutten, Bart P.F., Stein, Murray B., Ursano, Robert J., Vermetten, Eric, Vinkers, Christiaan H., Wang, Lin, Youssef, Nagy A., Marx, Christine, Grant, Gerry, Stein, Murray, Qin, Xue Jun, Jain, Sonia, McAllister, Thomas W., Zafonte, Ross, Lang, Ariel, Coimbra, Raul, Andaluz, Norberto, Shutter, Lori, George, Mark S., Brancu, Mira, Calhoun, Patrick S., Dedert, Eric, Elbogen, Eric B., Fairbank, John A., Hurley, Robin A., Kilts, Jason D., Kirby, Angela, Marx, Christine E., McDonald, Scott D., Moore, Scott D., Morey, Rajendra A., Naylor, Jennifer C., Rowland, Jared A., Swinkels, Cindy, Szabo, Steven T., Taber, Katherine H., Tupler, Larry A., Van Voorhees, Elizabeth E., Yoash-Gantz, Ruth E., Basu, Archana, Brick, Leslie A., Dalvie, Shareefa, Daskalakis, Nikolaos P., Ensink, Judith B.M., Hemmings, Sian M.J., Herringa, Ryan, Ikiyo, Sylvanus, Koen, Nastassja, Montalvo-Ortiz, Janitza, Nispeling, Danny, Pfeiffer, John, Schijven, Dick, Seedat, Soraya, Shinozaki, Gen, Sumner, Jennifer A., Swart, Patricia, Tyrka, Audrey, Van Zuiden, Mirjam, Wani, Agaz, Wolf, Erika J., Zannas, Anthony, Uddin, Monica, Nievergelt, Caroline M., ACS - Pulmonary hypertension & thrombosis, Graduate School, Adult Psychiatry, ARD - Amsterdam Reproduction and Development, Child Psychiatry, APH - Mental Health, ANS - Mood, Anxiety, Psychosis, Stress & Sleep, APH - Global Health, Psychiatry, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, Anatomy and neurosciences, MUMC+: MA Psychiatrie (3), Psychiatrie & Neuropsychologie, and RS: MHeNs - R3 - Neuroscience

Subjects
Male, 0301 basic medicine, Oncology, VA Mid-Atlantic MIRECC Workgroup, General Physics and Astronomy, medicine.disease_cause, IMMUNOLOGY, Epigenesis, Genetic, Stress Disorders, Post-Traumatic, Cohort Studies, Epigenome, chemistry.chemical_compound, POSTTRAUMATIC-STRESS-DISORDER, 0302 clinical medicine, Basic Helix-Loop-Helix Transcription Factors, Medicine, DNA METHYLATION, Kynurenine, Stress Disorders, Multidisciplinary, ASSOCIATION, Methylation, Post-Traumatic Stress Disorder (PTSD), Anxiety Disorders, Military Personnel, Mental Health, CpG site, Meta-analysis, DNA methylation, Female, ARYL-HYDROCARBON RECEPTOR, medicine.medical_specialty, Science, behavioral disciplines and activities, Article, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, AGE, Genetic, Clinical Research, Internal medicine, mental disorders, Genetics, Humans, EXPOSURE, Epigenetics, Post-traumatic stress disorder, PGC PTSD Epigenetics Workgroup, business.industry, PROFILES, General Chemistry, DNA Methylation, Immune dysregulation, Repressor Proteins, 030104 developmental biology, chemistry, Case-Control Studies, Post-Traumatic, Wounds and Injuries, Epigenetics analysis, business, 030217 neurology & neurosurgery, INTRuST Clinical Consortium, Epigenesis
Abstract

Epigenetic differences may help to distinguish between PTSD cases and trauma-exposed controls. Here, we describe the results of the largest DNA methylation meta-analysis of PTSD to date. Ten cohorts, military and civilian, contribute blood-derived DNA methylation data from 1,896 PTSD cases and trauma-exposed controls. Four CpG sites within the aryl-hydrocarbon receptor repressor (AHRR) associate with PTSD after adjustment for multiple comparisons, with lower DNA methylation in PTSD cases relative to controls. Although AHRR methylation is known to associate with smoking, the AHRR association with PTSD is most pronounced in non-smokers, suggesting the result was independent of smoking status. Evaluation of metabolomics data reveals that AHRR methylation associated with kynurenine levels, which are lower among subjects with PTSD. This study supports epigenetic differences in those with PTSD and suggests a role for decreased kynurenine as a contributor to immune dysregulation in PTSD., PTSD has been associated with DNA methylation of specific loci in the genome, but studies have been limited by small sample sizes. Here, the authors perform a meta-analysis of DNA methylation data from 10 different cohorts and identify CpGs in AHRR that are associated with PTSD.

Published
2020

26. 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 R.I., 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 M.J., 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 A.M., Lewis, Catrin E., Linnstaedt, Sarah D., Lori, Adriana, Lugonja, Bozo, Luykx, Jurjen J., Lyons, Michael J., Maples-Keller, Jessica, Marmar, Charles, Martin, Alicia R., Martin, Nicholas G., Maurer, Douglas, Mavissakalian, Matig R., McFarlane, Alexander, McGlinchey, Regina E., McLaughlin, Katie A., McLean, Samuel A., McLeay, Sarah, Mehta, Divya, Milberg, William P., Miller, Mark W., Morey, Rajendra A., Morris, Charles Phillip, Mors, Ole, Mortensen, Preben B., Neale, Benjamin M., 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., Ripke, Stephan, Risbrough, Victoria B., Roberts, Andrea L., Rothbaum, Alex O., Rothbaum, Barbara O., Roy-Byrne, Peter, Ruggiero, Ken, 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., Sumner, Jennifer A., 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 H., Voisey, Joanne, Wang, Yunpeng, Wang, Zhewu, Werge, Thomas, Williams, Michelle A., Williamson, Douglas E., Winternitz, Sherry, Wolf, Christiane, Wolf, Erika J., Wolff, Jonathan D., Yehuda, Rachel, Young, Ross Mc D., Young, Keith A., Zhao, Hongyu, Zoellner, Lori A., Liberzon, Israel, Ressler, Kerry J., Haas, Magali, Koenen, Karestan C., Nievergelt, Caroline M., Maihofer, Adam X., Klengel, Torsten, Atkinson, Elizabeth G., Chen, Chia Yen, Choi, Karmel W., Coleman, Jonathan R.I., 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 M.J., 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 A.M., Lewis, Catrin E., Linnstaedt, Sarah D., Lori, Adriana, Lugonja, Bozo, Luykx, Jurjen J., Lyons, Michael J., Maples-Keller, Jessica, Marmar, Charles, Martin, Alicia R., Martin, Nicholas G., Maurer, Douglas, Mavissakalian, Matig R., McFarlane, Alexander, McGlinchey, Regina E., McLaughlin, Katie A., McLean, Samuel A., McLeay, Sarah, Mehta, Divya, Milberg, William P., Miller, Mark W., Morey, Rajendra A., Morris, Charles Phillip, Mors, Ole, Mortensen, Preben B., Neale, Benjamin M., 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., Ripke, Stephan, Risbrough, Victoria B., Roberts, Andrea L., Rothbaum, Alex O., Rothbaum, Barbara O., Roy-Byrne, Peter, Ruggiero, Ken, 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., Sumner, Jennifer A., 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 H., Voisey, Joanne, Wang, Yunpeng, Wang, Zhewu, Werge, Thomas, Williams, Michelle A., Williamson, Douglas E., Winternitz, Sherry, Wolf, Christiane, Wolf, Erika J., Wolff, Jonathan D., Yehuda, Rachel, Young, Ross Mc D., Young, Keith A., Zhao, Hongyu, Zoellner, Lori A., Liberzon, Israel, Ressler, Kerry J., Haas, Magali, and Koenen, Karestan C.

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

28. 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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30. Cross-Disorder Genome-Wide Analyses Suggest a Complex Genetic Relationship Between Tourette Syndrome and Obsessive-Compulsive Disorder

Author

Yu, Dongmei, Mathews, Carol A., Scharf, Jeremiah M., Neale, Benjamin M., Davis, Lea K., Gamazon, Eric R., Derks, Eske M., Evans, Patrick, Edlund, Christopher K., Crane, Jacquelyn, Fagerness, Jesen A., Osiecki, Lisa, Gallagher, Patience, Gerber, Gloria, Haddad, Stephen, Illmann, Cornelia, McGrath, Lauren M., Mayerfeld, Catherine, Arepalli, Sampath, Barlassina, Cristina, Barr, Cathy L., Bellodi, Laura, Benarroch, Fortu, Berrió, Gabriel Bedoya, Bienvenu, O. Joseph, Black, Donald, Bloch, Michael H., Brentani, Helena, Bruun, Ruth D., Budman, Cathy L., Camarena, Beatriz, Campbell, Desmond D., Cappi, Carolina, Cardona Silgado, Julio C., Cavallini, Maria C., Chavira, Denise A., Chouinard, Sylvain, Cook, Edwin H., Cookson, M. R., Coric, Vladimir, Cullen, Bernadette, Cusi, Daniele, Delorme, Richard, Denys, Damiaan, Dion, Yves, Eapen, Valsama, Egberts, Karin, Falkai, Peter, Fernandez, Thomas, Fournier, Eduardo, Garrido, Helena, Geller, Daniel, Gilbert, Donald, Girard, Simon L., Grabe, Hans J., Grados, Marco A., Greenberg, Benjamin D., Gross-Tsur, Varda, Grünblatt, Edna, Hardy, John, Heiman, Gary A., Hemmings, Sian M.J., Herrera, Luis D., Hezel, Dianne M., Hoekstra, Pieter J., Jankovic, Joseph, Kennedy, James L., King, Robert A., Konkashbaev, Anuar I., Kremeyer, Barbara, Kurlan, Roger, Lanzagorta, Nuria, Leboyer, Marion, Leckman, James F., Lennertz, Leonhard, Liu, Chunyu, Lochner, Christine, Lowe, Thomas L., Lupoli, Sara, Macciardi, Fabio, Maier, Wolfgang, Manunta, Paolo, Marconi, Maurizio, McCracken, James T., Mesa Restrepo, Sandra C., Moessner, Rainald, Moorjani, Priya, Morgan, Jubel, Muller, Heike, Murphy, Dennis L., Naarden, Allan L., Ochoa, William Cornejo, Ophoff, Roel A., Pakstis, Andrew J., Pato, Michele T., Pato, Carlos N., Piacentini, John, Pittenger, Christopher, Pollak, Yehuda, Rauch, Scott L., Renner, Tobias, Reus, Victor I., Richter, Margaret A., Riddle, Mark A., Robertson, Mary M., Romero, Roxana, Rosário, Maria C., Rosenberg, David, Ruhrmann, Stephan, Sabatti, Chiara, Salvi, Erika, Sampaio, Aline S., Samuels, Jack, Sandor, Paul, Service, Susan K., Sheppard, Brooke, Singer, Harvey S., Smit, Jan H., Stein, Dan J., Strengman, Eric, Tischfield, Jay A., Turiel, Maurizio, Valencia Duarte, Ana V., Vallada, Homero, Veenstra-VanderWeele, Jeremy, Walitza, Susanne, Walkup, John, Wang, Ying, Weale, Mike, Weiss, Robert, Wendland, Jens R., Westenberg, Herman G.M., Yao, Yin, Hounie, Ana G., Miguel, Euripedes C., Nicolini, Humberto, Wagner, Michael, Ruiz-Linares, Andres, Cath, Danielle C., McMahon, William, Posthuma, Danielle, Oostra, Ben A., Nestadt, Gerald, Rouleau, Guy A., Purcell, Shaun, Jenike, Michael A., Heutink, Peter, Hanna, Gregory L., Conti, David V., Arnold, Paul D., Freimer, Nelson, Stewart, S. Evelyn, Knowles, James A., Cox, Nancy J., and Pauls, David L.

Subjects
Adult, Male, Psychiatric Status Rating Scales, Obsessive-Compulsive Disorder, Comorbidity, behavioral disciplines and activities, Polymorphism, Single Nucleotide, Severity of Illness Index, Article, mental disorders, Humans, Female, Genome-Wide Association Study, Tourette Syndrome
Abstract

Obsessive-compulsive disorder (OCD) and Tourette's syndrome are highly heritable neurodevelopmental disorders that are thought to share genetic risk factors. However, the identification of definitive susceptibility genes for these etiologically complex disorders remains elusive. The authors report a combined genome-wide association study (GWAS) of Tourette's syndrome and OCD.The authors conducted a GWAS in 2,723 cases (1,310 with OCD, 834 with Tourette's syndrome, 579 with OCD plus Tourette's syndrome/chronic tics), 5,667 ancestry-matched controls, and 290 OCD parent-child trios. GWAS summary statistics were examined for enrichment of functional variants associated with gene expression levels in brain regions. Polygenic score analyses were conducted to investigate the genetic architecture within and across the two disorders.Although no individual single-nucleotide polymorphisms (SNPs) achieved genome-wide significance, the GWAS signals were enriched for SNPs strongly associated with variations in brain gene expression levels (expression quantitative loci, or eQTLs), suggesting the presence of true functional variants that contribute to risk of these disorders. Polygenic score analyses identified a significant polygenic component for OCD (p=2×10(-4)), predicting 3.2% of the phenotypic variance in an independent data set. In contrast, Tourette's syndrome had a smaller, nonsignificant polygenic component, predicting only 0.6% of the phenotypic variance (p=0.06). No significant polygenic signal was detected across the two disorders, although the sample is likely underpowered to detect a modest shared signal. Furthermore, the OCD polygenic signal was significantly attenuated when cases with both OCD and co-occurring Tourette's syndrome/chronic tics were included in the analysis (p=0.01).Previous work has shown that Tourette's syndrome and OCD have some degree of shared genetic variation. However, the data from this study suggest that there are also distinct components to the genetic architectures of these two disorders. Furthermore, OCD with co-occurring Tourette's syndrome/chronic tics may have different underlying genetic susceptibility compared with OCD alone.

Published
2014

33. Cross-Disorder Genome-Wide Analyses Suggest a Complex Genetic Relationship Between Tourette’s Syndrome and OCD

Author

Yu, Dongmei, primary, Mathews, Carol A., additional, Scharf, Jeremiah M., additional, Neale, Benjamin M., additional, Davis, Lea K., additional, Gamazon, Eric R., additional, Derks, Eske M., additional, Evans, Patrick, additional, Edlund, Christopher K., additional, Crane, Jacquelyn, additional, Fagerness, Jesen A., additional, Osiecki, Lisa, additional, Gallagher, Patience, additional, Gerber, Gloria, additional, Haddad, Stephen, additional, Illmann, Cornelia, additional, McGrath, Lauren M., additional, Mayerfeld, Catherine, additional, Arepalli, Sampath, additional, Barlassina, Cristina, additional, Barr, Cathy L., additional, Bellodi, Laura, additional, Benarroch, Fortu, additional, Berrió, Gabriel Bedoya, additional, Bienvenu, O. Joseph, additional, Black, Donald W., additional, Bloch, Michael H., additional, Brentani, Helena, additional, Bruun, Ruth D., additional, Budman, Cathy L., additional, Camarena, Beatriz, additional, Campbell, Desmond D., additional, Cappi, Carolina, additional, Silgado, Julio C. Cardona, additional, Cavallini, Maria C., additional, Chavira, Denise A., additional, Chouinard, Sylvain, additional, Cook, Edwin H., additional, Cookson, M.R., additional, Coric, Vladimir, additional, Cullen, Bernadette, additional, Cusi, Daniele, additional, Delorme, Richard, additional, Denys, Damiaan, additional, Dion, Yves, additional, Eapen, Valsama, additional, Egberts, Karin, additional, Falkai, Peter, additional, Fernandez, Thomas, additional, Fournier, Eduardo, additional, Garrido, Helena, additional, Geller, Daniel, additional, Gilbert, Donald L., additional, Girard, Simon L., additional, Grabe, Hans J., additional, Grados, Marco A., additional, Greenberg, Benjamin D., additional, Gross-Tsur, Varda, additional, Grünblatt, Edna, additional, Hardy, John, additional, Heiman, Gary A., additional, Hemmings, Sian M.J., additional, Herrera, Luis D., additional, Hezel, Dianne M., additional, Hoekstra, Pieter J., additional, Jankovic, Joseph, additional, Kennedy, James L., additional, King, Robert A., additional, Konkashbaev, Anuar I., additional, Kremeyer, Barbara, additional, Kurlan, Roger, additional, Lanzagorta, Nuria, additional, Leboyer, Marion, additional, Leckman, James F., additional, Lennertz, Leonhard, additional, Liu, Chunyu, additional, Lochner, Christine, additional, Lowe, Thomas L., additional, Lupoli, Sara, additional, Macciardi, Fabio, additional, Maier, Wolfgang, additional, Manunta, Paolo, additional, Marconi, Maurizio, additional, McCracken, James T., additional, Mesa Restrepo, Sandra C., additional, Moessner, Rainald, additional, Moorjani, Priya, additional, Morgan, Jubel, additional, Muller, Heike, additional, Murphy, Dennis L., additional, Naarden, Allan L., additional, Nurmi, Erika, additional, Ochoa, William Cornejo, additional, Ophoff, Roel A., additional, Pakstis, Andrew J., additional, Pato, Michele T., additional, Pato, Carlos N., additional, Piacentini, John, additional, Pittenger, Christopher, additional, Pollak, Yehuda, additional, Rauch, Scott L., additional, Renner, Tobias, additional, Reus, Victor I., additional, Richter, Margaret A., additional, Riddle, Mark A., additional, Robertson, Mary M., additional, Romero, Roxana, additional, Rosário, Maria C., additional, Rosenberg, David, additional, Ruhrmann, Stephan, additional, Sabatti, Chiara, additional, Salvi, Erika, additional, Sampaio, Aline S., additional, Samuels, Jack, additional, Sandor, Paul, additional, Service, Susan K., additional, Sheppard, Brooke, additional, Singer, Harvey S., additional, Smit, Jan H., additional, Stein, Dan J., additional, Strengman, Eric, additional, Tischfield, Jay A., additional, Turiel, Maurizio, additional, Valencia Duarte, Ana V., additional, Vallada, Homero, additional, Veenstra-VanderWeele, Jeremy, additional, Walitza, Susanne, additional, Wang, Ying, additional, Weale, Mike, additional, Weiss, Robert, additional, Wendland, Jens R., additional, Westenberg, Herman G.M., additional, Shugart, Yin Yao, additional, Hounie, Ana G., additional, Miguel, Euripedes C., additional, Nicolini, Humberto, additional, Wagner, Michael, additional, Ruiz-Linares, Andres, additional, Cath, Danielle C., additional, McMahon, William, additional, Posthuma, Danielle, additional, Oostra, Ben A., additional, Nestadt, Gerald, additional, Rouleau, Guy A., additional, Purcell, Shaun, additional, Jenike, Michael A., additional, Heutink, Peter, additional, Hanna, Gregory L., additional, Conti, David V., additional, Arnold, Paul D., additional, Freimer, Nelson B., additional, Stewart, S. Evelyn, additional, Knowles, James A., additional, Cox, Nancy J., additional, and Pauls, David L., additional

Published
2015
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34. Serotonin transporter variants play a role in anxiety sensitivity in South African adolescents.

Author

Hemmings, Sian M.J., Martin, Lindi I., van der Merwe, Lize, Benecke, Rohan, Domschke, Katharina, and Seedat, Soraya

Subjects
*ANXIETY sensitivity, *TEENAGERS, *GENOTYPE-environment interaction, *SEROTONIN, *POST-traumatic stress disorder
Abstract

Objectives: Anxiety sensitivity (AS) has predictive potential for the development of anxiety disorders. We investigated the role that gene–environment (G × E) interactions, focussing on childhood trauma (CT) and selectedSLC6A4variants, play in modulating levels of AS in a South African adolescent population.Methods: All adolescents (n = 951) completed measures for AS and CT. SixSLC6A4polymorphisms were genotyped. G × E influences on AS levels were assessed using multiple linear regression models. Relevant confounders were included in all analyses.Results: Xhosa (n = 634) and Coloured (n = 317) participants were analysed independently of one another. The5-HTTLPR-rs25531L-Ghaplotype associated with reduced AS among Xhosa adolescents (P = 0.010). In addition, the rs1042173CC-genotype protected against increased levels of AS in Xhosa participants who had experienced increased levels of CT (P = 0.038). Coloured males homozygous for theS-allele had significantly increased levels of AS compared to Coloured males with at least oneL-allele (P = 0.016).Conclusions: This is the first study to be conducted on AS in adolescents from two ethnically diverse populations. Results indicate that theL-Ghaplotype confers protection against high AS levels in a Xhosa population. Furthermore, increased CT was found to protect against high levels of AS in Xhosa rs1042173CC-carriers. [ABSTRACT FROM PUBLISHER]

Published
2016
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