Identification of Novel, Replicable Genetic Risk Loci for Suicidal Thoughts and Behaviors Among US Military Veterans

作者：Nathan A. Kimbrel, Allison E. Ashley‐Koch, Xuejun Qin, Jennifer H. Lindquist, Melanie E. Garrett, Michelle F. Dennis, Lauren P. Hair, Jennifer E. Huffman, Daniel Jacobson, Ravi Madduri, Jodie Trafton, Hilary Coon, Anna R. Docherty, Niamh Mullins, Douglas M. Ruderfer, Philip D. Harvey, Benjamin H. McMahon, David W. Oslin, Jean C. Beckham, Elizabeth R. Hauser, Michael A. Hauser, Khushbu Agarwal, Allison E. Ashley‐Koch, Mihaela Aslan, Jean C. Beckham, Edmond Begoli, Tanmoy Bhattacharya, Ben Brown, Patrick S. Calhoun, Kei‐Hoi Cheung, Sutanay Choudhury, Ashley Cliff, Judith D. Cohn, Silvia Crivelli, Leticia Cuellar-Hengartner, Haedi E. Deangelis, Michelle F. Dennis, Sayera Dhaubhadel, Patrick D. Finley, Kumkum Ganguly, Michael R. Garvin, Joel Gelernter, Lauren P. Hair, P.D. Harvey, Elizabeth R. Hauser, Michael A. Hauser, Nicolas Hengartner, Daniel Jacobson, Piet Jones, David Kainer, Alan D. Kaplan, Ira R. Katz, Rachel L. Kember, Nathan A. Kimbrel, Angela C. Kirby, John C. Ko, Beauty Kolade, John Lagergren, Matthew Lane, Daniel Levey, Drew Levin, Jennifer H. Lindquist, Xianlian Liu, Ravi Madduri, Carrie Manore, Susana B. Martins, John F. McCarthy, Mikaela McDevitt-Cashman, Benjamin H. McMahon, Izaak Miller, Destinee Morrow, David W. Oslin, Mirko Pavicic-Venegas, John Pestian, Saiju Pyarajan, Xuejun Qin, Nallakkandi Rajeevan, Christine M. Ramsey, Ruy M. Ribeiro, Alex A Rodriguez, Jonathan Romero, Daniel Santel, Noah Schaefferkoetter, Yunling Shi, Murray B. Stein, Kyle A. Sullivan, Ning Sun, Suzanne Tamang, Alice Townsend, Jodie Trafton, Angelica M. Walker, Xian-Ge Wang, Victoria Wangia-Anderson, Renji Yang, Hong‐Jun Yoon, Shinjae Yoo, Rafael Zamora‐Resendiz, Hongyu Zhao, Anna R. Docherty, Niamh Mullins, Jonathan R. I. Coleman, Andrey A. Shabalin, Jooeun Kang, Balasz Murnyak, Frank R. Wendt, Mark J. Adams, Adrián I. Campos, Emily DiBlasi, Janice M. Fullerton, Henry R. Kranzler, Amanda V. Bakian, Eric T. Monson, Miguel E. Rentería, Ole A. Andreassen, Cynthia M. Bulik, Howard J. Edenberg, Ronald C. Kessler, J. John Mann, John I. Nürnberger, Giorgio Pistis, Fabian Streit, Robert J. Ursano, Swapnil Awasthi, Andrew W. Bergen, Wade H. Berrettini, Martin Bohus, Harry Brandt, Xiao Chang, Hsi‐Chung Chen, Wei J. Chen, Erik D. Christensen, Steven Crawford, Scott J. Crow, Philibert Duriez, Alexis C. Edwards, Fernando Fernández‐Aranda, Manfred M. Fichter, Hanga Galfalvy, Steven Gallinger, Michael J. Gandal, Philip Gorwood, Yiran Guo, Jonathan D. Hafferty, Håkon Håkonarson, Katherine A. Halmi, Akitoyo Hishimoto, Sonia Jain, Stéphane Jamain, Susana Jiménez‐Múrcia, Craig Johnson, Allan S. Kaplan, Walter H. Kaye, Pamela K. Keel, James L. Kennedy, Minsoo Kim, Kelly L. Klump, Daniel Levey, Dong Li, Shih‐Cheng Liao, Klaus Lieb, Lisa Lilenfeld, Adriana Lori, Pierre J. Magistretti, Christian R. Marshall, James E. Mitchell, R Myers, Satoshi Okazaki, Ikuo Otsuka, Dalila Pinto, Abigail Powers, Nicolás Ramoz, Stephan Ripke, Stefan Roepke, Vsevolod Rozanov, Stephen W. Scherer, Christian Schmahl, Marcus Sokolowski, Anna Starnawska, Michael Strober, Mei‐Hsin Su, Laura M. Thornton, Janet Treasure, Erin B. Ware, Hunna J. Watson, Stephanie H. Witt, D. Blake Woodside, Zeynep Yılmaz, Lea Zillich, Esben Agerbo, Anders D. Børglum, Gerome Breen, Ditte Demontis, Annette Erlangsen, Tõnu Esko, Joel Gelernter, Stephen J. Glatt, David M. Hougaard, Hai‐Gwo Hwu, Po‐Hsiu Kuo, Cathryn M. Lewis, Qingqin S. Li, Chih‐Min Liu, Nicholas G. Martin, Andrew M. McIntosh, Sarah E. Medland, Ole Mors, Merete Nordentoft, John I. Nürnberger, Catherine M. Olsen, David J. Porteous, Daniel J. Smıth, Eli A. Stahl, Murray B. Stein, Danuta Wasserman, Thomas Werge, David C. Whiteman, Virginia L. Willour, Hilary Coon, Douglas M. Ruderfer, Eric A. Dedert, Eric B. Elbogen, John A. Fairbank, Robin A. Hurley, Jason D. Kilts, Sarah L. Martindale, Christine E. Marx, Scott D. McDonald, Scott D. Moore, Rajendra A. Morey, Jennifer C. Naylor, Jared A. Rowland, Robert D. Shura, Cindy Swinkels, Larry A. Tupler, Elizabeth E. Van Voorhees, Ruth E. Yoash-Gantz, J. Michael Gaziano, Sumitra Muralidhar, Rachel Ramoni, Kyong‐Mi Chang, Christopher J. O’Donnell, Philip S. Tsao, James L. Breeling, Elizabeth R. Hauser, Yan V. Sun, Grant D. Huang, Juan P. Casas, Jennifer Moser, Stacey B. Whitbourne, Jessica V. Brewer, T. Conner, Dean P. Argyres, Brady Stephens, Mary T. Brophy, Donald E. Humphries, Luis E. Selva, Nhan Do, Shahpoor Shayan, Kelly Cho, Lori Churby, Peter W.F. Wilson, Rachel McArdle, Louis J. Dell’Italia, Kristin Mattocks, John B. Harley, Jeff Whittle, Frank J. Jacono, John A. Wells, Salvador Gutierrez, Gretchen Gibson, Kimberly Hammer, Laurence S. Kaminsky, Gerardo Villareal, Scott Kinlay, Junzhe Xu, Mark B. Hamner, Roy O. Mathew, Sujata Bhushan, Pran Iruvanti, Michael Godschalk, Zuhair K. Ballas, Douglas Ivins, Stephen Mastorides, Jonathan P. Moorman, Saib Gappy, Jon Klein, Nora Ratcliffe, Hermes Flórez, Olaoluwa Okusaga, Maureen Murdoch, Peruvemba Sriram, Shing Shing Yeh, Neeraj Tandon, Darshana Jhala, Suthat Liangpunsakul, Kris Ann Oursler, Mary A. Whooley, Sunil K. Ahuja, Joseph Constans, Paul Meyer, Jennifer Greco, Michael Rauchman, Richard J. Servatius, Melinda Gaddy, Agnes Wallbom, Timothy R. Morgan, Todd Stapley, Scott E. Sherman, George Ross, Patrick Strollo, Edward J. Boyko, Laurence Meyer, Samir Gupta, Mostaqul Huq, Joseph Fayad, Adriana M. Hung, Jack Lichy, Robin A. Hurley, R. Brooks Robey, Rob Striker · 发表于：JAMA Psychiatry · 年份：2022 · DOI：10.1001/jamapsychiatry.2022.3896 · 被引用次数：57 · 研究领域：Genetic Associations and Epidemiology、Suicide and Self-Harm Studies、Mental Health via Writing

Importance: Suicide is a leading cause of death; however, the molecular genetic basis of suicidal thoughts and behaviors (SITB) remains unknown. Objective: To identify novel, replicable genomic risk loci for SITB. Design, Setting, and Participants: This genome-wide association study included 633 778 US military veterans with and without SITB, as identified through electronic health records. GWAS was performed separately by ancestry, controlling for sex, age, and genetic substructure. Cross-ancestry risk loci were identified through meta-analysis. Study enrollment began in 2011 and is ongoing. Data were analyzed from November 2021 to August 2022. Main Outcome and Measures: SITB. Results: A total of 633 778 US military veterans were included in the analysis (57 152 [9%] female; 121 118 [19.1%] African ancestry, 8285 [1.3%] Asian ancestry, 452 767 [71.4%] European ancestry, and 51 608 [8.1%] Hispanic ancestry), including 121 211 individuals with SITB (19.1%). Meta-analysis identified more than 200 GWS (P < 5 × 10-8) cross-ancestry risk single-nucleotide variants for SITB concentrated in 7 regions on chromosomes 2, 6, 9, 11, 14, 16, and 18. Top single-nucleotide variants were largely intronic in nature; 5 were independently replicated in ISGC, including rs6557168 in ESR1, rs12808482 in DRD2, rs77641763 in EXD3, rs10671545 in DCC, and rs36006172 in TRAF3. Associations for FBXL19 and AC018880.2 were not replicated. Gene-based analyses implicated 24 additional GWS cross-ancestry ris...