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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
neuroscience
The Relationship of Attention-Deficit/Hyperactivity Disorder With Posttraumatic Stress Disorder: A Two-Sample Mendelian Randomization and Population-Based Sibling Comparison Study
Biological Psychiatry, Volume 93, No. 4, Year 2023
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Description
Background: Attention-deficit/hyperactivity disorder (ADHD) and posttraumatic stress disorder (PTSD) are associated, but it is unclear if this is a causal relationship or confounding. We used genetic analyses and sibling comparisons to clarify the direction of this relationship. Methods: Linkage disequilibrium score regression and 2-sample Mendelian randomization were used to test for genetic correlation (rg) and bidirectional causal effects using European ancestry genome-wide association studies of ADHD (20,183 cases and 35,191 controls) and 6 PTSD definitions (up to 320,369 individuals). Several additional variables were included in the analysis to verify the independence of the ADHD-PTSD relationship. In a population-based sibling comparison (N = 2,082,118 individuals), Cox regression models were fitted to account for time at risk, a range of sociodemographic factors, and unmeasured familial confounders (via sibling comparisons). Results: ADHD and PTSD had consistent rg (rg range, 0.43–0.52; p < .001). ADHD genetic liability was causally linked with increased risk for PTSD (β = 0.367; 95% CI, 0.186–0.552; p = 7.68 × 10−5). This result was not affected by heterogeneity, horizontal pleiotropy (Mendelian randomization Egger intercept = 4.34 × 10−4, p = .961), or other phenotypes and was consistent across PTSD datasets. However, we found no consistent associations between PTSD genetic liability and ADHD risk. Individuals diagnosed with ADHD were at a higher risk for developing PTSD than their undiagnosed sibling (hazard ratio = 2.37; 95% CI, 1.98–3.53). Conclusions: Our findings add novel evidence supporting the need for early and effective treatment of ADHD, as patients with this diagnosis are at significantly higher risk to develop PTSD later in life. © 2022 Society of Biological Psychiatry
Authors & Co-Authors
Wendt, Frank R.
United States, New Haven
Yale School of Medicine
United States, West Haven
Va Connecticut Healthcare System
Canada, Toronto
University of Toronto
Valdimarsdottir, Unnur Anna
Iceland, Reykjavik
Haskoli Islands
Sweden, Stockholm
Karolinska Institutet
United States, Boston
Harvard T.h. Chan School of Public Health
Gelernter, Joel E.
United States, New Haven
Yale School of Medicine
United States, West Haven
Va Connecticut Healthcare System
Stein, Murray B.
United States, La Jolla
University of California, San Diego
United States, San Diego
Human Longevity, Inc.
United States, San Diego
Va San Diego Healthcare System
Nivard, Michel G.
Netherlands, Amsterdam
Vrije Universiteit Amsterdam
Maihofer, Adam X.
United States, La Jolla
University of California, San Diego
United States, San Diego
Va San Diego Healthcare System
Choi, Karmel W.
Unknown Affiliation
Coleman, Jonathan R.I.
Unknown Affiliation
Daskalakis, Nikolaos P.
Unknown Affiliation
Denckla, Christy A.
Unknown Affiliation
Ketema, Elizabeth
Unknown Affiliation
Morey, Rajendra A.
Unknown Affiliation
Polimanti, Renato
United States, New Haven
Yale School of Medicine
United States, West Haven
Va Connecticut Healthcare System
Ratanatharathorn, Andrew D.
Unknown Affiliation
Torres, Katy
Unknown Affiliation
Wingo, Aliza P.
Unknown Affiliation
Zai, Clement C.
Unknown Affiliation
Aiello, Allison E.
Unknown Affiliation
Almli, Lynn M.
Unknown Affiliation
Amstadter, Ananda Beth
Unknown Affiliation
Andersen, Søren Bo
Unknown Affiliation
Andreassen, Ole Andreas
Unknown Affiliation
Arbisi, Paul A.
Unknown Affiliation
Ashley-Koch, Allison E.
Unknown Affiliation
Austin, Sydney Bryn
Unknown Affiliation
Avdibegović, Esmina
Unknown Affiliation
BØRglum, Anders Dupont
Unknown Affiliation
Babić, Dragan
Unknown Affiliation
Baekvad-Hansen, Marie
Unknown Affiliation
Baker, Dewleen G.
Unknown Affiliation
Beckham, Jean C.
Unknown Affiliation
Bierut, Laura Jean
Unknown Affiliation
Bisson, Jonathan I.
Unknown Affiliation
Boks, Marco P.M.
Unknown Affiliation
Bolger, Elizabeth A.
Unknown Affiliation
Bradley-Davino, Bekh B.
Unknown Affiliation
Brashear, Meghan M.
Unknown Affiliation
Breen, Gerome
Unknown Affiliation
Bryant, Richard A.
Unknown Affiliation
Bustamante, Angela C.
Unknown Affiliation
Bybjerg-Grauholm, Jonas
Unknown Affiliation
Calabrese, Joseph R.
Unknown Affiliation
Caldas-de-Almeida, José M.
Unknown Affiliation
Chen, Chia Yen
Unknown Affiliation
Dale, Anders M.
Unknown Affiliation
Dalvie, Shareefa
Unknown Affiliation
Deckert, Jürgen
Unknown Affiliation
Delahanty, Douglas L.
Unknown Affiliation
Dennis, Michelle F.
Unknown Affiliation
Disner, Seth G.
Unknown Affiliation
Domschke, Katharina
Unknown Affiliation
Duncan, Laramie E.
Unknown Affiliation
Kulenović, Alma Džubur
Unknown Affiliation
Erbes, Christopher R.
Unknown Affiliation
Evans, Alexandra
Unknown Affiliation
Feeny, Norah C.
Unknown Affiliation
Flory, Janine Dyck
Unknown Affiliation
Forbes, David
Unknown Affiliation
Franz, Carol E.
Unknown Affiliation
Galea, Sandro
Unknown Affiliation
Garrett, Melanie E.
Unknown Affiliation
Gautam, Aarti
Unknown Affiliation
Gelaye, Bizu S.
Unknown Affiliation
Geuze, Elbert
Unknown Affiliation
Gillespie, Charles F.
Unknown Affiliation
Uka, Afërdita Goçi
Unknown Affiliation
Gordon, Scott D.
Unknown Affiliation
Guffanti, Guia
Unknown Affiliation
Hammamieh, Rasha
Unknown Affiliation
Hauser, Michael A.
Unknown Affiliation
Heath, Andrew Christopher
Unknown Affiliation
Hemmings, Sian Megan Joanna
Unknown Affiliation
Hougaard, David Michael
Unknown Affiliation
Jakovljević, Miro
Unknown Affiliation
Jett, Marti
Unknown Affiliation
Johnson, Eric Otto
Unknown Affiliation
Jones, Ian Richard G.
Unknown Affiliation
Jovanović, Tanja
Unknown Affiliation
Qin, Xuejun
Unknown Affiliation
Karstoft, Karen Inge
Unknown Affiliation
Kaufman, Milissa L.
Unknown Affiliation
Kessler, Ronald C.
Unknown Affiliation
Khan, Alaptagin
Unknown Affiliation
Kimbrel, Nathan A.
Unknown Affiliation
King, Anthony P.J.
Unknown Affiliation
Koen, Nastassja
Unknown Affiliation
Kranzler, Henry R.
Unknown Affiliation
Kremen, William S.
Unknown Affiliation
Lawford, Bruce Robert
Unknown Affiliation
Lebois, Lauren A.M.
Unknown Affiliation
Lewis, Catrin E.
Unknown Affiliation
Liberzon, Israel
Unknown Affiliation
Linnstaedt, Sarah D.
Unknown Affiliation
Logue, Mark W.
Unknown Affiliation
Lori, Adriana
Unknown Affiliation
Lugonja, Božo
Unknown Affiliation
Luykx, Jurjen Justin
Unknown Affiliation
Lyons, Michael J.
Unknown Affiliation
Maples-Keller, Jessica L.
Unknown Affiliation
Marmar, Charles Raymond
Unknown Affiliation
Martin, Nicholas G.
Unknown Affiliation
Maurer, Douglas M.
Unknown Affiliation
Mavissakalian, Matig R.
Unknown Affiliation
McFarlane, Alexander Cowell
Unknown Affiliation
McGlinchey, Regina E.
Unknown Affiliation
McLaughlin, Katie A.
Unknown Affiliation
McLean, Samuel A.
Unknown Affiliation
Mellor, Rebecca
Unknown Affiliation
Michopoulos, V. J.
Unknown Affiliation
Milberg, William P.
Unknown Affiliation
Miller, Mark W.
Unknown Affiliation
Morris, Charles Phillip
Unknown Affiliation
Mors, Ole N.
Unknown Affiliation
Mortensen, Preben Bo
Unknown Affiliation
Nordentoft, Merete
Unknown Affiliation
O'Donnell, Meaghan L.
Unknown Affiliation
Panizzon, Matthew S.
Unknown Affiliation
Peverill, Matthew
Unknown Affiliation
Pietrzak, Robert H.
Unknown Affiliation
Rice, John P.
Unknown Affiliation
Risbrough, Victoria B.
Unknown Affiliation
Roberts, Andrea L.
Unknown Affiliation
Rothbaum, Alex O.
Unknown Affiliation
Rothbaum, Barbara Olasov
Unknown Affiliation
Roy-Byrne, Peter P.
Unknown Affiliation
Ruggiero, Kenneth J.
Unknown Affiliation
Rutten, Bart PF F.
Unknown Affiliation
Saccone, Nancy L.
Unknown Affiliation
Sánchez, Sixto E.
Unknown Affiliation
Schijven, Dick
Unknown Affiliation
Seedat, Soraya
Unknown Affiliation
Seligowski, Antonia V.
Unknown Affiliation
Sheerin, Christina M.
Unknown Affiliation
Silove, Derrick M.
Unknown Affiliation
Smith, Alicia K.
Unknown Affiliation
Smoller, Jordan Wassertheil
Unknown Affiliation
Sponheim, Scott R.
Unknown Affiliation
Stein, Dan J.
Unknown Affiliation
Teicher, Martin Hersch
Unknown Affiliation
Thompson, Wesley Kurt
Unknown Affiliation
Uddin, Monica
Unknown Affiliation
Ursano, Robert J.
Unknown Affiliation
van den Heuvel, Leigh Luella
Unknown Affiliation
Van Hooff, Miranda L.
Unknown Affiliation
Vermetten, E. H.G.J.M.
Unknown Affiliation
Vinkers, Christiaan H.
Unknown Affiliation
Voisey, J.
Unknown Affiliation
Werge, Thomas M.
Unknown Affiliation
Williams, Michelle A.
Unknown Affiliation
Winternitz, Sherry R.
Unknown Affiliation
Wolf, Christiane
Unknown Affiliation
Wolf, Erika J.
Unknown Affiliation
Yehuda, Rachel
Unknown Affiliation
Young, Ross Mc Donald
Unknown Affiliation
Zhao, Hongyu
Unknown Affiliation
Zoellner, Lori A.
Unknown Affiliation
Haas, Magali
Unknown Affiliation
Provost, Allison C.
Unknown Affiliation
Salem, Rany M.
Unknown Affiliation
Shaffer, Richard A.
Unknown Affiliation
Ripke, Stephan
Unknown Affiliation
Daly, Mark J.
Unknown Affiliation
Ressler, Kerry James
Unknown Affiliation
Koenen, Karestan Chase
Unknown Affiliation
Nievergelt, Caroline M.
United States, La Jolla
University of California, San Diego
United States, San Diego
Va San Diego Healthcare System
Larsson, Henrik
Sweden, Orebro
Faculty of Medicine and Health
Sweden, Stockholm
Karolinska Institutet
Mattheisen, M.
Canada, Halifax
Dalhousie University
Germany, Munich
Ludwig-maximilians-universität München
Statistics
Citations: 9
Authors: 167
Affiliations: 13
Identifiers
Doi:
10.1016/j.biopsych.2022.08.012
ISSN:
00063223
Research Areas
Environmental
Genetics And Genomics
Mental Health
Study Design
Randomised Control Trial
Cross Sectional Study