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Jarick, Ivonne ; Volckmar, Anna-Lena ; Pütter, Carolin ; Pechlivanis, Sonali ; Nguyen, Trang T. ; Dauvermann, Maria R. ; Beck, Sebastian ; Albayrak, Özgür ; Scherag, Susann ; Gilsbach, Susanne ; Cichon, Sven ; Hoffmann, Per ; Degenhardt, Franziska ; Nöthen, Markus Maria ; Schreiber, Stefan ; Wichmann, Heinz Erich ; Jöckel, Karl-Heinz ; Heinrich, Joachim ; Tiesler, Carla Marie Thérèse ; Faraone, Stephen V. ; Walitza, Susanne ; Sinzig, Judith ; Freitag, Christine M. ; Meyer, Jobst ; Herpertz-Dahlmann, Beate ; Lehmkuh, Gerd ; Renner, Tobias J. ; Warnke, Andreas ; Romanos, Marcel ; Lesch, Klaus-Peter J. ; Reif, Andreas ; Schimmelmann, Benno G. ; Hebebrand, Johannes ; Scherag, André ; Hinney, Anke
Attention-deficit/hyperactivity disorder (ADHD) is a common, highly heritable neurodevelopmental disorder. Genetic loci have not yet been identified by genome-wide association studies. Rare copy number variations (CNVs), such as chromosomal deletions or duplications, have been implicated in ADHD and other neurodevelopmental disorders. To identify rare (frequency ≤1%) CNVs that increase the risk of ADHD, we performed a whole-genome CNV analysis based on 489 young ADHD patients and 1285 adult population-based controls and identified one significantly associated CNV region. In tests for a global burden of large (>500 kb) rare CNVs, we observed a nonsignificant (P=0.271) 1.126-fold enriched rate of subjects carrying at least one such CNV in the group of ADHD cases. Locus-specific tests of association were used to assess if there were more rare CNVs in cases compared with controls. Detected CNVs, which were significantly enriched in the ADHD group, were validated by quantitative (q)PCR. Findings were replicated in an independent sample of 386 young patients with ADHD and 781 young population-based healthy controls. We identified rare CNVs within the parkinson protein 2 gene (PARK2) with a significantly higher prevalence in ADHD patients than in controls (P=2.8 × 10(-4) after empirical correction for genome-wide testing). In total, the PARK2 locus (chr 6: 162 659 756-162 767 019) harboured three deletions and nine duplications in the ADHD patients and two deletions and two duplications in the controls. By qPCR analysis, we validated 11 of the 12 CNVs in ADHD patients (P=1.2 × 10(-3) after empirical correction for genome-wide testing). In the replication sample, CNVs at the PARK2 locus were found in four additional ADHD patients and one additional control (P=4.3 × 10(-2)). Our results suggest that copy number variants at the PARK2 locus contribute to the genetic susceptibility of ADHD. Mutations and CNVs in PARK2 are known to be associated with Parkinson disease.
Faraone, Stephen V. ; Banaschewski, Tobias ; Coghill, David ; Zheng, Yi ; Biederman, Joseph ; Bellgrove, Mark A. ; Newcorn, Jeffrey H. ; Gignac, Martin ; Al Saud, Nouf M. ; Manor, Iris ; Rohde, Luis Augusto ; Yang, Li ; Cortese, Samuele ; Almagor, Doron ; Stein, Mark A. ; Albatti, Turki H. ; Aljoudi, Haya F. ; Alqahtani, Mohammed M.J. ; Asherson, Philip ; Atwoli, Lukoye ; Bölte, Sven ; Buitelaar, Jan K. ; Crunelle, Cleo L. ; Daley, David ; Dalsgaard, Søren ; Döpfner, Manfred ; Espinet, Stacey ; Fitzgerald, Michael ; Franke, Barbara ; Gerlach, Manfred ; Haavik, Jan ; Hartman, Catharina A. ; Hartung, Cynthia M. ; Hinshaw, Stephen P. ; Hoekstra, Pieter J. ; Hollis, Chris ; Kollins, Scott H. ; Kooij, Johanna Jacoba Sandra ; Kuntsi, Jonna ; Larsson, Henrik ; Li, Tingyu ; Liu, Jing ; Merzon, Eugene ; Mattingly, Gregory ; Mattos, Paulo ; McCarthy, Suzanne ; Mikami, Amori Yee ; Molina, Brooke S.G. ; Nigg, Joel T. ; Purper-Ouakil, Diane ; Omigbodun, Olayinka O. ; Polanczyk, Guilherme V. ; Pollak, Yehuda ; Poulton, Alison S. ; Reif, Andreas ; Rajkumar, Ravi Philip ; Rubia, Katya ; Reding, Andrew ; Rucklidge, Julia ; Romanos, Marcel ; Ramos-Quiroga, J. Antoni ; Schellekens, Arnt ; Scheres, Anouk ; Schoeman, Renata ; Schweitzer, Julie B. ; Shah, Henal ; Solanto, Mary V. ; Sonuga-Barke, Edmund ; Soutullo, César ; Steinhausen, Hans-Christoph ; Swanson, James M. ; Thapar, Anita ; Tripp, Gail ; Glind, Geurt van de ; Brink, Wim van den ; Oord, Saskia van der ; Venter, Andre ; Vitiello, Benedetto ; Walitza, Susanne ; Wang, Yufeng
Background: Misconceptions about ADHD stigmatize affected people, reduce credibility of providers, and prevent/delay treatment. To challenge misconceptions, we curated findings with strong evidence base. Methods: We reviewed studies with more than 2000 participants or meta-analyses from five or more studies or 2000 or more participants. We excluded meta-analyses that did not assess publication bias, except for meta-analyses of prevalence. For network meta-analyses we required comparison adjusted funnel plots. We excluded treatment studies with waiting-list or treatment as usual controls. From this literature, we extracted evidence-based assertions about the disorder. Results: We generated 208 empirically supported statements about ADHD. The status of the included statements as empirically supported is approved by 80 authors from 27 countries and 6 continents. The contents of the manuscript are endorsed by 366 people who have read this document and agree with its contents. Conclusions: Many findings in ADHD are supported by meta-analysis. These allow for firm statements about the nature, course, outcome causes, and treatments for disorders that are useful for reducing misconceptions and stigma.
Mapping cortical brain asymmetry in 17,141 healthy individuals worldwide via the ENIGMA Consortium
(2017)
Kong, Xiang-Zhen ; Mathias, Samuel R. ; Guadalupe, Tulio ; Abé, Christoph ; Agartz, Ingrid ; Akudjedu, Theophilus N. ; Andre, Aleman ; Saud, Alhusaini ; Allen, Nicholas B. ; Ames, David ; Andreassen, Ole A. ; Arias Vásquez, Alejandro ; Armstrong, Nicola J. ; Bergo, Felipe ; Bastin, Mark E. ; Batalla, Albert ; Bauer, Jochen ; Baune, Bernhard T. ; Baur, Ramona ; Biederman, Joseph ; Blaine, Sara K. ; Boedhoe, Premika ; Bøen, Erlend ; Bose, Anushree ; Bralten, Janita ; Brandeis, Daniel ; Brem, Silvia ; Brodaty, Henry ; Bröhl, Henrieke ; Brooks, Samantha J. ; Buitelaar, Jan K. ; Bürger, Christian ; Bülow, Robin ; Calhoun, Vince D. ; Calvo, Anna ; Canales-Rodrı́guez, Erick Jorge ; Canive, Jose M. ; Cannon, Dara M. ; Caparelli, Elisabeth C. ; Castellanos, Francisco X. ; Cavalleri, Gianpiero L. ; Cendes, Fernando ; Chaim-Avancini, Tiffany Moukbel ; Chantiluke, Kaylita ; Chen, Qun-lin ; Chen, Xiayu ; Cheng, Yuqi ; Christakou, Anastasia ; Clark, Vincent P. ; Coghill, David ; Connolly, Colm G. ; Conzelmann, Annette ; Cόrdova-Palomera, Aldo ; Cousijn, Janna ; Crow, Tim ; Cubillo, Ana ; Dannlowski, Udo ; de Bruttopilo, Sara Ambrosino ; Zeeuw, Patrick de ; Deary, Ian J. ; Delanty, Norman ; Demeter, Damion V. ; Di Martino, Adriana ; Dickie, Erin W ; Dietsche, Bruno ; Doan, N. Trung ; Doherty, Colin P. ; Doyle, Alysa ; Durston, Sarah ; Earl, Eric ; Ehrlich, Stefan ; Ekman, Carl Johan ; Elvsåshagen, Torbjørn ; Epstein, Jeffery N. ; Fair, Damien A. ; Faraone, Stephen V. ; Fatouros-Bergman, Helena ; Fernndez, Guillen ; Busatto Filho, Geraldo ; Flyckt, Lena ; Forster, Katharina ; Jean-Paul, Fouche ; Foxe, John J. ; Fuentes-Claramonte, Paola ; Fullerton, Janice M. ; Garavan, Hugh ; Garcia, Danielle do Santos ; Gotlib, Ian H. ; Goudriaan, Anna E. ; Grabe, Hans Jörgen ; Groenewold, Nynke A. ; Grotegerd, Dominik ; Gruber, Oliver ; Gurholt, Tiril ; Haavik, Jan ; Hahn, Tim ; Hansell, Narelle K. ; Harris, Mathew A. ; Hartman, Catharina ; Hernandez, Maria del Carmen Valdes ; Heslenfeld, Dirk ; Hester, Robert ; Hibar, Derrek Paul ; Ho, Beng-Choon ; Ho, Tiffany C. ; Hoekstra, Pieter J. ; van Holst, Ruth J. ; Hoogman, Martine ; Hovik, Marie F. ; Howells, Fleur M. ; Hugdahl, Kenneth ; Huyser, Chaim ; Ingvar, Martind ; Irwin, Lourdes ; Ishikawa, Akari ; James, Anthony ; Jahanshad, Neda ; Jernigan, Terry L. ; Jönsson, Erik G. ; Kahler, Claas ; Kaleda, Vasily ; Kelly, Clare ; Kerich, Michael ; Keshavan, Matcheri S ; Khadka, Sabin ; Kircher, Tilo ; Kohls, Gregor ; Konrad, Kerstin ; Korucuoglu, Ozlem ; Krämer, Bernd ; Krug, Axel ; Kwon, Jun Soo ; Lambregts-Rommelse, Nanda ; Landén, Mikael ; Lázaro, Luisa ; Lebedeva, Irina ; Lenroot, Rhoshel ; Lesch, Klaus-Peter J. ; Li, Qinqin ; Lim, Kelvin O. ; Liu, Jia ; Lochner, Christine ; London, Edythe D. ; Lonning, Vera ; Lorenzetti, Valentina ; Luciano, Michelle ; Luijten, Maartje ; Lundervold, Astri J. ; Mackey, Scott ; MacMaster, Frank P. ; Maingault, Sophie ; Malpas, Charles B. ; Malt, Ulrik F. ; Mataix-Cols, David ; Martin-Santos, Rocio ; Mayer, Andrew R. ; McCarthy, Hazel ; Mitchell, Philip B. ; Mueller, Bryon A. ; Maniega, Susana Munoz ; Mazoyer, Bernard ; McDonald, Colm ; McLellan, Quinn ; McMahon, Katie L. ; McPhilemy, Genevieve ; Momenan, Reza ; Morales, Angelica M. ; Narayanaswamy, Janardhanan C. ; Moreira, José Carlos Vasques ; Nerland, Stener ; Nestor, Liam ; Nigg, Joel T. ; Nordvik, Jan-Egil ; Novotny, Stephanie ; Oberwelland, Eileen ; O’Gorman, Ruth L. ; Oosterlaan, Jaap ; Oranje, Bob ; Orr, Catherine ; Overs, Bronwyn ; Pauli, Paul ; Paulus, Martin ; Plessen, Kerstin ; Polier, Georg von ; Pomarol-Clotet, Edith ; Qiu, Jiang ; Radua, Joaquim ; Ramos-Quiroga, J. Antoni ; Reddy, Y.C. Janardhan ; Reif, Andreas ; Roberts, Gloria ; Rosa, Pedro ; Rubia, Katya ; Sacchet, Matthew D. ; Sachdev, Perminder S. ; Salvador, Raymond ; Schmaal, Lianne ; Schweren, Lisanne ; Seidman, Larry J. ; Seitz, Jochen ; Serpa, Mauricio Henriques ; Shaw, Philip ; Shumskaya, Elena ; Silk, Timothy J. ; Simmons, Alan N. ; Simulionyte, Egle ; Sinha, Rajita ; Sjoerds, Zsuzsika ; Smelror, Runar Elle ; Soliva, Joan Carlos ; Solowij, Nadia ; Sponheim, Scott R. ; Stein, Dan J. ; Stein, Elliot A. ; Stevens, Michael ; Strike, Lachlan T. ; Sudre, Gustavo ; Sui, Jing ; Tamm, Leanne ; Temmingh, Hendrik S. ; Thoma, Robert J. ; Tomyshev, Alexander S. ; Tronchin, Giulia ; Turner, Jessica A. ; Uhlmann, Anne ; van Erp, Theo G.M. ; van den Heuvel, Odile ; Meer, Dennis van der ; Eijk, Liza van ; Vance, Alasdair ; Veer, Ilya M. ; Veltman, Dick J. ; Venkatasubramanian, Ganesan ; Vilarroya, Oscar ; Vives-Gilabert, Yolanda ; Voineskos, Aristotle N. ; Völzke, Henry ; Vuletic, Daniella ; Walitza, Susanne ; Walter, Henrik ; Walton, Esther ; Wardlaw, Joanna M. ; Wen, Wei ; Westlye, Lars T. ; Whelan, Christopher D. ; White, Tonya ; Wiers, Reinout W. ; Wright, Margaret J. ; Wittfeld, Katharina ; Yang, Tony T. ; Yasuda, Clarissa L. ; Yoncheva, Yuliya ; Yucel, Murat ; Yun, Je-Yeon ; Zanetti, Marcus Vinicius ; Zhen, Zonglei ; Zhu, Xing-xing ; Ziegler, Georg Christoph ; Zierhut, Kathrin ; De Zubicaray, Greig ; Zwiers, Marcel P. ; Glahn, David C. ; Franke, Barbara ; Crivello, Fabrice ; Tzourio-Mazoyer, Nathalie ; Fisher, Simon E. ; Thompson, Paul M. ; Francks, Clyde ; Farde, Lars ; Engberg, Goran ; Erhardt, Sophie ; Cervenka, Simon ; Schwieler, Lilly ; Piehl, Fredrik ; Collste, Karin ; Victorsson, Pauliina ; Malmqvist, Anna ; Hedberg, Mikael ; Orhan, Funda
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