Identifying gene-environment interactions in schizophrenia: Contemporary challenges for integrated, large-scale investigations

Jim Van Os, Bart P. Rutten, Inez Myin-Germeys, Philippe Delespaul, Wolfgang Viechtbauer, Catherine Van Zelst, Richard Bruggeman, Ulrich Reininghaus, Craig Morgan, Robin M. Murray, Marta Di Forti, Philip McGuire, Lucia R. Valmaggia, Matthew J. Kempton, Charlotte Gayer-Anderson, Kathryn Hubbard, Stephanie Beards, Simona A. Stilo, Adanna Onyejiaka, Francois BourqueGemma Modinos, Stefania Tognin, Maria Calem, Michael C. O'Donovan, Michael J. Owen, Peter Holmans, Nigel Williams, Nicholas Craddock, Alexander Richards, Isla Humphreys, Andreas Meyer-Lindenberg, F. Markus Leweke, Heike Tost, Ceren Akdeniz, Cathrin Rohleder, J. Malte Bumb, Emanuel Schwarz, Köksal Alptekin, Alp Üçok, Meram Can Saka, E. Cem Atbagoǧlu, Sinan Gülöksüz, Guvem Gumus-Akay, Burçin Cihan, Hasan Karadaǧ, Haldan Soygür, Eylem Şahin Cankurtaran, Semra Ulusoy, Berna Akdede, Tolga Binbay, Ahmet Ayer, Handan Noyan, Gülgah Karadayi, Elçin Akturan, Halis Ulaş, Celso Arango, Mara Parellada, Miquel Bernardo, Julio Sanjuan, Julio Bobes, Manuel Arrojo, J.L. Santos, Pedro Cuadrado, José Juan Rodríguez Solano, A. Carracedo, Bernardo Núñez García, Lorena Roldan Martin, Gladys Lopez, B. Cabrera, Sónia Cruz, E. M. Díaz Mesa, María Pouso, Eduard Jimenez, T. Sanchez, Marta Rapado, E. Gonzalez, C. Martinez, E. Sanchez, Maria Soledad Olmeda, Lieuwe de Haan, Eva Velthorst, Mark van der Gaag, Debby Van Dam, Els van der Ven, Floor Van Der Meer, Elles Messchaert, Tamar C. Kraan, Nadine Burger, Marion Leboyer, Anita Szoke, Franck Schürhoff, Pierre Michel Llorca, Stéphane Jamain, Andrea Tortelli, Flora Frijda, Jeanne Vilain, Anne Marie Galliot, Grégoire Baudin, Aziz Ferchiou, Richard J. Ross, E Bulzacka, T Charpeaud, A.M. Tronche, Marc De Hert, Ruud Van Winkel, Jeroen Decoster, C. Derom, E. Thiery, N.C Stefanis, G Sachs, H. Aschauer, I Lasser, B Winklbaur, M Schlögelhofer, Anita Riecher-Rössler, Stefan Borgwardt, Amibel Walter, F Harrisberger, Renata Smieskova, Charlotte Rapp, Sarah Ittig, F Soguel-dit-Piquard, Erich Studerus, Joachim Klosterkötter, Stephan Ruhrmann, P. Paruch, D Julkowski, D Hilboll, P. C. Sham, S.S Cherny, Eric Y.H. Chen, Daniel Campbell, M Li, C.M. Romeo Casabona, A. Emaldi Cirión, A. Urruela Mora, P. Jones, James B. Kirkbride, M. Cannon, D. Rujescu, I. Tarricone, D. Berardi, Enzo Bonora, Marco Seri, T. Marcacci, L Chiri, F. Chierzi, V. Storbini, M. Braca, M.G. Minenna, I. Donegani, Angelo Fioritti, D La Barbera , Caterina La Cascia, A Mulè, L Sideli, R. Sartorio, L. Ferraro, G. Tripoli, F. Seminerio, M. Marinaro, Patrick McGorry, Barnaby Nelson, G. Paul Amminger, C Pantelis, Paulo Rossi Menezes, Cristina Marta Del-Ben, S.H. Gallo Tenan, R. Shuhama, M Ruggeri, Sarah Tosato, Antonio Lasalvia, C. Bonetto, E. Ira, Merete Nordentoft, Marie Odile Krebs, Neus Barrantes-Vidal, , Paula Cristobal Narvaez, Thomas R. Kwapil, Elisa Brietzke, Rodrigo A. Bressan, Ary Gadelha, Nadja P. Maric, Sanja Andric Petrovic, Marina M. Mihaljevic, Tijana Mirjanic

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174 Citations (Scopus)

Abstract

Recent years have seen considerable progress in epidemiological and molecular genetic research into environmental and genetic factors in schizophrenia, but methodological uncertainties remain with regard to validating environmental exposures, and the population risk conferred by individual molecular genetic variants is small. There are now also a limited number of studies that have investigated molecular genetic candidate gene-environment interactions (G × E), however, so far, thorough replication of findings is rare and G × E research still faces several conceptual and methodological challenges. In this article, we aim to review these recent developments and illustrate how integrated, large-scale investigations may overcome contemporary challenges in G × E research, drawing on the example of a large, international, multi-center study into the identification and translational application of G × E in schizophrenia. While such investigations are now well underway, new challenges emerge for G × E research from late-breaking evidence that genetic variation and environmental exposures are, to a significant degree, shared across a range of psychiatric disorders, with potential overlap in phenotype. © 2014 The Author.
Original languageEnglish
Pages (from-to)729-736
JournalSchizophrenia Bulletin
Volume40
DOIs
Publication statusPublished - 1 Jan 2014

Keywords

  • epidemiology
  • gene-environment interaction
  • genetics
  • psychosis
  • schizophrenia

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