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

Van Os, J.; Rutten, B. P.; Myin-Germeys, I.; Delespaul, P.; Viechtbauer, W.; Van Zelst, C.; Bruggeman, R.; Reininghaus, U.; Morgan, C.; Murray, R. M.; Di Forti, M.; McGuire, P.; Valmaggia, L. R.; Kempton, M. J.; Gayer-Anderson, C.; Hubbard, K.; Beards, S.; Stilo, S. A.; Onyejiaka, A.; Bourque, F.; Modinos, G.; Tognin, S.; Calem, M.; O'Donovan, M. C.; Owen, M. J.; Holmans, P.; Williams, N.; Craddock, N.; Richards, A.; Humphreys, I.; Meyer-Lindenberg, A.; Leweke, F. M.; Tost, H.; Akdeniz, C.; Rohleder, C.; Bumb, J. M.; Schwarz, E.; Alptekin, K.; Üçok, A.; Saka, M. C.; Atbagoǧlu, E. C.; Gülöksüz, S.; Gumus-Akay, G.; Cihan, B.; Karadaǧ, H.; Soygür, H.; Cankurtaran, E. S.; Ulusoy, S.; Akdede, B.; Binbay, T.; Ayer, A.; Noyan, H.; Karadayi, G.; Akturan, E.; Ulaş, H.; Arango, C.; Parellada, M.; Bernardo, M.; Sanjuán, J.; Bobes, J.; Arrojo Romero, Manuel; Santos, J. L.; Cuadrado, P.; Solano, J. J. R.; Carracedo Álvarez, Ángel; Bernardo, E. G.; Roldán, L.; López, G.; Cabrera, B.; Cruz, S.; Mesa, E. M. D.; Pouso, M.; Jiménez, E.; Sánchez, T.; Rapado, M.; González, E.; Martínez, C.; Sánchez, E.; Olmeda, M. S.; De Haan, L.; Velthorst, E.; Van Der Gaag, M.; Selten, J. P.; Van Dam, D.; Van Der Ven, E.; Van Der Meer, F.; Messchaert, E.; Kraan, T.; Burger, N.; Leboyer, M.; Szoke, A.; Schürhoff, F.; Llorca, P. M.; Jamain, S.; Tortelli, A.; Frijda, F.; Vilain, J.; Galliot, A. M.; Baudin, G.; Ferchiou, A.; Richard, J. R.; Bulzacka, E.; Charpeaud, T.; Tronche, A. M.; De Hert, M.; Van Winkel, R.; Decoster, J.; Derom, C.; Thiery, E.; Stefanis, N. C.; Sachs, G.; Aschauer, H.; Lasser, I.; Winklbaur, B.; Schlögelhofer, M.; Riecher-Rössler, A.; Borgwardt, S.; Walter, A.; Harrisberger, F.; Smieskova, R.; Rapp, C.; Ittig, S.; Soguel-Dit-Piquard, F.; Studerus, E.; Klosterkötter, J.; Ruhrmann, S.; Paruch, J.; Julkowski, D.; Hilboll, D.; Sham, P. C.; Cherny, S. S.; Chen, E. Y. H.; Campbell, D. D.; Li, M.; Romeo-Casabona, C. M.; Cirión, A. E.; Mora, A. U.; Jones, P.; Kirkbride, J.; Cannon, M.; Rujescu, D.; Tarricone, I.; Berardi, D.; Bonora, E.; Seri, M.; Marcacci, T.; Chiri, L.; Chierzi, F.; Storbini, V.; Braca, M.; Minenna, M. G.; Donegani, I.; Fioritti, A.; La Barbera, D.; La Cascia, C. E.; Mulè, A.; Sideli, L.; Sartorio, R.; Ferraro, L.; Tripoli, G.; Seminerio, F.; Marinaro, A. M.; McGorry, P.; Nelson, B.; Amminger, G. P.; Pantelis, C.; Menezes, P. R.; Del-Ben, C. M.; Tenan, S. H. G.; Shuhama, R.; Ruggeri, M.; Tosato, S.; Lasalvia, A.; Bonetto, C.; Ira, E.; Nordentoft, M.; Krebs, M. O.; Barrantes-Vidal, N.; Cristóbal, P.; Kwapil, T. R.; Brietzke, E.; Bressan, R. A.; Gadelha, A.; Maric, N. P.; Andric, S.; Mihaljevic, M.; Mirjanic, T.
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URI: http://hdl.handle.net/20.500.11940/225
PMID: 24860087
DOI: 10.1093/schbul/sbu069
ISSN: 0586-7614
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Texto completo disponible por cortesía de Schizophr Bull . 2014 Jul;40(4):729-36. doi: 10.1093/schbul/sbu069. (904.8Kb)
Date issued
2014
Journal title
SCHIZOPHRENIA BULLETIN
Type of content
Artigo
MeSH
Gene-Environment Interaction | Genetic Predisposition to Disease | Humans | Schizophrenia | Schizophrenic Psychology | Social Environment
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.

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