Details

Autor(en) / Beteiligte

• Maihofer, Adam X.
• Daskalakis, Nikolaos P.
• Denckla, Christy A.
• Ketema, Elizabeth
• Morey, Rajendra A.
• Torres, Katy
• Aiello, Allison E.
• Almli, Lynn M.
• Austin, S. Bryn
• Borglum, Anders D.
• Babić, Dragan
• Beckham, Jean C.
• Bisson, Jonathan I.
• Boks, Marco P.
• Bryant, Richard A.
• Bustamante, Angela C.
• Caldas-de-Almeida, José M.
• Chen, Chia-Yen
• Dale, Anders M.
• Deckert, Jürgen
• Delahanty, Douglas L.
• Domschke, Katharina
• Džubur Kulenović, Alma
• Erbes, Christopher R.
• Farrer, Lindsay A.
• Flory, Janine D.
• Forbes, David
• Franz, Carol E.
• Gautam, Aarti
• Gelaye, Bizu
• Geuze, Elbert
• Gillespie, Charles F.
• Goçi, Aferdita
• Guffanti, Guia
• Hauser, Michael A.
• Heath, Andrew C.
• Hemmings, Sian M.J.
• Hougaard, David Michael
• Jett, Marti
• Qin, Xue-Jun
• Karstoft, Karen-Inge
• Kaufman, Milissa L.
• Kessler, Ronald C.
• Koen, Nastassja
• Kranzler, Henry R.
• Kremen, William S.
• Lawford, Bruce R.
• Liberzon, Israel
• Lori, Adriana
• Lugonja, Božo
• Luykx, Jurjen J.
• Marmar, Charles
• Martin, Nicholas G.
• Maurer, Douglas
• Mavissakalian, Matig R.
• McFarlane, Alexander
• McLean, Samuel A.
• Mellor, Rebecca
• Michopoulos, Vasiliki
• Milberg, William
• Morris, Charles Phillip
• Nelson, Elliot C.
• Nordentoft, Merete
• Norman, Sonya B.
• O’Donnell, Meaghan
• Peterson, Alan L.
• Pietrzak, Robert H.
• Roberts, Andrea L.
• Rothbaum, Barbara O.
• Rung, Ariane
• Sanchez, Sixto E.
• Schijven, Dick
• Seedat, Soraya
• Seng, Julia S.
• Sheerin, Christina M.
• Silove, Derrick
• Smith, Alicia K.
• Smoller, Jordan W.
• Sponheim, Scott R.
• Stein, Dan J.
• Teicher, Martin H.
• Thompson, Wesley K.
• van den Heuvel, Leigh Luella
• Van Hooff, Miranda
• Vinkers, Christiaan H.
• Wang, Yunpeng
• Wang, Zhewu
• Williams, Michelle A.
• Winternitz, Sherry
• Wolf, Christiane
• Wolf, Erika J.
• Young, Ross McD
• Zhao, Hongyu
• Zoellner, Lori A.
• Provost, Allison C.
• Sebat, Jonathan
• Shaffer, Richard A.
• Koenen, Karestan C.
• Stein, Murray B.
• Nievergelt, Caroline M.

Titel

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

Ist Teil von

• Biological psychiatry (1969), 2022-04, Vol.91 (7), p.626-636

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2022

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• 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). 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. 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. 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.