Enhancing Discovery of Genetic Variants for Posttraumatic Stress Disorder Through Integration of Quantitative Phenotypes and Trauma Exposure Information.
Обработка статьи · этапы, ошибки и управление
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
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 H, 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, Nievergelt Caroline M
Аннотация
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.