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, Koksal Alptekin, Alp Ucok, Meram Can Saka, E. Cem Atbasoglu, Sinan Guloksuz, Guvem Gumus-Akay, Burin Cihan, Hasan Karadag, Haldan Soygur, Eylem Sahin Cankurtaran, Semra Ulusoy, Berna Akdede, Tolga Binbay, Ahmet Ayer, Handan Noyan, Gulsah Karadayi, Elin Akturan, Halis Ulas, Celso Arango, Mara Parellada, Miguel Bernardo, Julio Sanjuan, Julio Bobes, Manuel Arrojo, Jose Luis Santos, Pedro Cuadrado, Jose Juan Rodriguez Solano, Angel Carracedo, Enrique Garcia Bernardo, Laura Roldan, Gonzalo Lopez, Bibiana Cabrera, Sabrina Cruz, Eva Ma Diaz Mesa, Maria Pouso, Estela Jimenez, Teresa Sanchez, Marta Rapado, Emiliano Gonzalez, Covadonga Martinez, Emilio Sanchez, Ma Soledad Olmeda, Lieuwe de Haan, Eva Velthorst, Mark van der Gaag, Jean-Paul Selten, Daniella van Dam, Elsje van der Ven, Floor van der Meer, Elles Messchaert, Tamar Kraan, Nadine Burger, Marion Leboyer, Andrei Szoke, Franck Schurhoff, Pierre-Michel Llorca, Stephane Jamain, Andrea Tortelli, Flora Frijda, Jeanne Vilain, Anne-Marie Galliot, Gregoire Baudin, Aziz Ferchiou, Jean-Romain Richard, Ewa Bulzacka, Thomas Charpeaud, Anne-Marie Tronche, Marc De Hert, Ruud van Winkel, Jeroen Decoster, Catherine Derom, Evert Thiery, Nikos C. Stefanis, Gabriele Sachs, Harald Aschauer, Iris Lasser, Bernadette Winklbaur, Monika Schlogelhofer, Anita Riecher-Rossler, Stefan Borgwardt, Anna Walter, Fabienne Harrisberger, Renata Smieskova, Charlotte Rapp, Sarah Ittig, Fabienne Soguel-Dit-Piquard, Erich Studerus, Joachim Klosterkotter, Stephan Ruhrmann, Julia Paruch, Dominika Julkowski, Desiree Hilboll, Pak C. Sham, Stacey S. Cherny, Eric Y. H. Chen, Desmond D. Campbell, Miaoxin Li, Carlos Maria Romeo-Casabona, Aitziber Emaldi Cirion, Asier Urruela Mora, Peter Jones, James Kirkbride, Mary Cannon, Dan Rujescu, Ilaria Tarricone, Domenico Berardi, Elena Bonora, Marco Seri, Thomas Marcacci, Luigi Chiri, Federico Chierzi, Viviana Storbini, Mauro Braca, Maria Gabriella Minenna, Ivonne Donegani, Angelo Fioritti, Daniele La Barbera, Caterina Erika La Cascia, Alice Mule, Lucia Sideli, Rachele Sartorio, Laura Ferraro, Giada Tripoli, Fabio Seminerio, Anna Maria Marinaro, Patrick McGorry, Barnaby Nelson, G. Paul Amminger, Christos Pantelis, Paulo R. Menezes, Cristina M. Del-Ben, Silvia H. Gallo Tenan, Rosana Shuhama, Mirella Ruggeri, Sarah Tosato, Antonio Lasalvia, Chiara Bonetto, Elisa Ira, Merete Nordentoft, Marie-Odile Krebs, Neus Barrantes-Vidal, Paula Cristobal, Thomas R. Kwapil, Elisa Brietzke, Rodrigo A. Bressan, Ary Gadelha, Nadja P. Maric, Sanja Andric, Marina Mihaljevic, Tijana Mirjanic

*Corresponding author for this work

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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 x E), however, so far, thorough replication of findings is rare and G x 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 x E research, drawing on the example of a large, international, multi-center study into the identification and translational application of G x E in schizophrenia. While such investigations are now well underway, new challenges emerge for G x 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.
Original languageEnglish
Pages (from-to)729-736
JournalSchizophrenia Bulletin
Volume40
Issue number4
DOIs
Publication statusPublished - Jul 2014

Keywords

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

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