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

作者：N. Kimbrel, A. Ashley-Koch, Xue-Jun Qin, J. Lindquist, M. Garrett, M. Dennis, Lauren P. Hair, Jennifer E. Huffman, D. Jacobson, Ravi K. Madduri, Jodie Trafton, H. Coon, Anna R. Docherty, N. Mullins, D. Ruderfer, Philip D. Harvey, B. McMahon, D. Oslin, J. Beckham, E. Hauser, M. Hauser, Khushbu Agarwal, A. Ashley-Koch, M. Aslan, J. Beckham, Edmon Begoli, Tanmoy Bhattacharya, Ben Brown, P. Calhoun, Kei-Hoi Cheung, Sutanay Choudhury, A. Cliff, J. Cohn, S. Crivelli, Leticia Cuellar-Hengartner, Haedi E DeAngelis, M. Dennis, S. Dhaubhadel, Patrick D. Finley, Kumkum Ganguly, Michael R. Garvin, J. Gelernter, Lauren P. Hair, P. Harvey, E. Hauser, Mike Hauser, N. Hengartner, D. Jacobson, Piet C. Jones, D. Kainer, A. Kaplan, I. Katz, R. Kember, N. Kimbrel, A. Kirby, John Ko, Beauty Kolade, J. Lagergren, M. Lane, D. Levey, Drew Levin, J. Lindquist, Xian-Liang Liu, Ravi K. Madduri, Carrie Manore, S. B. Martins, J. Mccarthy, Mikaela McDevitt-Cashman, B. McMahon, Izaak Miller, D. Morrow, D. Oslin, Mirko Pavicic-Venegas, J. Pestian, S. Pyarajan, X. Qin, N. Rajeevan, C. Ramsey, Ruy M. Ribeiro, Alex Rodriguez, Jonathan Romero, D. Santel, Noah Schaefferkoetter, Yun-Ling Shi, Murray B. Stein, K. Sullivan, Ning Sun, Suzanne R. Tamang, Alice O. Townsend, Jodie Trafton, A. Walker, Xian-Ge Wang, Victoria Wangia-Anderson, Renji Yang, Hong-Jun Yoon, S. Yoo, R. Zamora-Resendiz, Hongyu Zhao, Anna R. Docherty, N. Mullins, J. Coleman, A. Shabalin, Jooeun Kang, Balasz Murnyak, F. Wendt, M. Adams, A. Campos, Emily DiBlasi, J. Fullerton, H. Kranzler, A. Bakian, Eric T. Monson, Miguel E. Rentería, O. Andreassen, C. Bulik, H. Edenberg, R. Kessler, J. Mann, J. Nurnberger, G. Pistis, F. Streit, R. Ursano, S. Awasthi, A. Bergen, W. Berrettini, M. Bohus, H. Brandt, Xiao Chang, Hsi-Chung Chen, Wei J. Chen, Erik D. Christensen, S. Crawford, S. Crow, P. Duriez, Alexis C. Edwards, F. Fernández-Aranda, M. Fichter, H. Galfalvy, S. Gallinger, Michael Jeffrey Gandal, P. Gorwood, Yiran Guo, J. Hafferty, H. Hakonarson, K. Halmi, A. Hishimoto, Sonia Jain, S. Jamain, S. Jiménez-Murcia, Craig Johnson, A. Kaplan, W. Kaye, P. Keel, James L. Kennedy, Minsoo Kim, K. Klump, D. Levey, Dong Li, Shih-Cheng Liao, K. Lieb, L. Lilenfeld, A. Lori, P. Magistretti, C. Marshall, James E. Mitchell, R. Myers, Satoshi Okazaki, Ikuo Otsuka, Dalila Pinto, A. Powers, N. Ramoz, S. Ripke, S. Roepke, V. Rozanov, S. Scherer, C. Schmahl, M. Sokolowski, A. Starnawska, M. Strober, Mei-Hsin Su, L. Thornton, J. Treasure, E. Ware, Hunna J. Watson, S. Witt, D. Woodside, Zeynep Yilmaz, L. Zillich, E. Agerbo, A. Børglum, G. Breen, D. Demontis, A. Erlangsen, T. Esko, J. Gelernter, S. Glatt, D. Hougaard, H. Hwu, Po-Hsiu Kuo, C. Lewis, Qingqin S. Li, Chih-Min Liu, N. G. Martin, A. McIntosh, S. Medland, O. Mors, M. Nordentoft, J. Nurnberger, C. Olsen, D. Porteous, Daniel J. Smith, E. Stahl, Murray B. Stein, D. Wasserman, T. Werge, D. Whiteman, Virginia L. Willour, H. Coon, D. Ruderfer, Eric A Dedert, Eric B. Elbogen, J. Fairbank, R. Hurley, J. Kilts, S. Martindale, C. Marx, S. McDonald, Scott D. Moore, R. Morey, J. Naylor, J. Rowland, R. Shura, Cindy M. Swinkels, Larry A. Tupler, Elizabeth E. Van Voorhees, R. Yoash-Gantz, J. Gaziano, S. Muralidhar, R. Ramoni, Kyong-Mi Chang, Christopher J. O’Donnell, Philip S. Tsao, Jim L. Breeling, Elizabeth R. Hauser, Yan Sun, Grant Huang, J. Casas, J. Moser, Stacey B. Whitbourne, Jessica V. V. Brewer, Tod Conner, Dean P. Argyres, B. Stephens, M. Brophy, Donald E. Humphries, Luis E. Selva, Nhan V. Do, S. Shayan, Kelly Cho, Lori L Churby, P. Wilson, Rachel McArdle, Louis J. Dellitalia, Kristin M. Mattocks, J. Harley, J. Whittle, F. Jacono, J. Wells, Salvador Gutiérrez, G. Gibson, Kim Hammer, Laurence S. Kaminsky, Gerardo Villareal, S. Kinlay, Junzhe Xu, M. Hamner, R. Mathew, Sujata Bhushan, Pran R. Iruvanti, M. Godschalk, Z. Ballas, D. Ivins, Stephen M. Mastorides, J. Moorman, S. Gappy, J. Klein, N. Ratcliffe, H. Flórez, O. Okusaga, M. Murdoch, P. Sriram, S. Yeh, Neeraj Tandon, D. Jhala, S. Liangpunsakul, K. Oursler, M. Whooley, S. Ahuja, Joseph I. Constans, Paul Meyer, Jennifer A. Greco, M. Rauchman, R. Servatius, M. Gaddy, A. Wallbom, Timothy Morgan, T. Stapley, Scott Sherman, George A. L. Ross, P. Strollo, E. Boyko, Laurence Meyer, Samir K. Gupta, Mostaqul Huq, Joseph M. Fayad, A. Hung, J. Lichy, R. Hurley, B. Robey, Robert T. Striker · 发表于：JAMA psychiatry · 年份：2022 · DOI：10.1001/jamapsychiatry.2022.3896 · 被引用次数：51 · 研究领域：Medicine

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 ...