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, Stefan Borgwardt

*Corresponding author for this work
174 Citations (Scopus)


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.

Original languageEnglish
JournalSchizophrenia bulletin
Issue number4
Pages (from-to)729-736
Number of pages8
Publication statusPublished - 07.2014


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