Identifying Gene-Environment Interactions in Schizophrenia: Contemporary Challenges for Integrated, Large-scale Investigations

ŞahinCankurtaran, Eylem; van der Gaa, Mark; van Os, Jim; Rutten, Bart P.; Van Os, J.; van Zelst, Catherine; Viechtbauer, Wolfgang; van der Ven, Elsje; Myin-Germeys, Inez; Van Zelst, C.; van der Meer, Floor; de Haan, Lieuwe; Reininghaus, Ulrich; van Dam, Daniella; Morgan, Craig; van Winkel, Ruud; Murray, Robin M.; O’Donovan, Michael C.; McGuire, Philip; Valmaggia, Lucia R.; Kempton, Matthew J.; Sartorio, Crocettarachele; Ucok, Alp; Stilo, Simona A.; Onyejiaka, Adanna; Modinos, Gemma; Karadag, Hasan; Tognin, Stefania; Sartorio, R.; O'Donovan, Michael C.; Rm, Murray; Owen, Michael J.; Sartorio, Rachele; Williams, Nigel; Paul Amminger, G.; Richards, Alexander; Pm, Llorca; Delespaul, Philippe; Meyer-Lindenberg, Andreas; Mc, O'Donovan; Leweke, F. Markus; Mj, Owen; Bruggeman, Richard; Tost, Heike; Luis Santos, Jose; Rohleder, Cathrin; Rodriguez Solano, Jose Juan; Lr, Valmaggia; Di Forti, Marta; Schwarz, Emanuel; Jm, Bumb; Üçok, Alp; Mj, Kempton; Saka, Meram Can; Gayer-Anderson, Charlotte; Mc, Saka; Hubbard, Kathryn; T.), Mirjanic; Pc, Sham; Beards, Stephanie; Sa, Stilo; Karadağ, Hasan; Soygür, Haldan; Ss, Cherny; Ulusoy, Semra; Bourque, Francois; Sanchez, Teresa; Sanchez, Emilio; Calem, Maria; Noyan, Handan; Karadayı, Gülşah; Jl, Santos; Ulaş, Halis; Jj, Rodríguez Solano; Holmans, Peter; Parellada, Mara; Craddock, Nicholas; Sanjuán, Julio; Humphreys, Isla; Schurhoff, Franck; Santos, Jose Luis; López, Gonzalo; Solano, José Juan Rodríguez; Akdeniz, Ceren; Roldán, Laura; Lopez, Gonzalo; Bumb, J. Malte; Alptekin, Köksal; Mesa, Eva Mª Díaz; Ms, Olmeda; Pouso, María; Markus Leweke, F.; Gülöksüz, Sinan; Jp, Selten; Gumus-Akay, Guvem; Atbagoǧlu, E. C.; Sánchez, Teresa; Rapado, Marta; Cihan, Burçin; Pr, Menezes; Martínez, Covadonga; Sánchez, Emilio; Sh, Gallo Tenan; Cankurtaran, Eylem Sahin; Velthorst, Eva; Olmeda, Mª Soledad; Akdede, Berna; Malte Bumb, J.; Binbay, Tolga; Ayer, Ahmet; Van Der Gaag, M.; Jr, Richard; Selten, Jean-Paul; Van Dam, D.; Akturan, Elçin; Van Der Ven, E.; Tr, Kwapil; Van Der Meer, F.; Arango, Celso; Messchaert, Elles; Ra, Bressan; Bernardo, M.; Kraan, Tamar; Nc, Stefanis; Bobes, Julio; Leboyer, Marion; Urruela Mora, Asier; Arrojo, Manuel; Szoke, Andrei; Schürhoff, Franck; Cuadrado, Pedro; Maria Romeo-Casabona, Carlos; Llorca, Pierre-Michel; Carracedo, Angel; Vilain, Jeanne; Bernardo, Enrique García; Tortelli, Andrea; Mg, Minenna; Cabrera, Bibiana; Cruz, Sabrina; Jiménez, Estela; Richard, Jean-Romain; González, Emiliano; Mo, Krebs; Tronche, Anne-Marie; Van Winkel, R.; De Haan, L.; Np, Maric; Thiery, Evert; Stefanis, Nikos C.; Nc Docks, at The University of North Carolina at Greensboro; Sachs, Gabriele; Winklbaur, Bernadette; Natl, European Network; Lasser, Iris; Burger, Nadine; Others,; Schlögelhofer, Monika; Walter, Anna; Riecher-Rössler, Anita; Jamain, Stéphane; Frijda, Flora; Smieskova, Renata; Galliot, Anne-Marie; Rapp, Charlotte; Baudin, Grégoire; Ferchiou, Aziz; Soguel-Dit-Piquard, Fabienne; Bulzacka, Ewa; Studerus, Erich; Klosterkötter, Joachim; Charpeaud, Thomas; Ruhrmann, Stephan; De Hert, Marc; Paruch, Julia; Julkowski, Dominika; Decoster, Jeroen; Sham, Pak C.; Derom, Catherine; Guloksuz, Sinan; Li, Miaoxin; Romeo-Casabona, Carlos María; Gei), European Network of National Networks studying Gene Environment Interactions in Schizophrenia (EU; Aschauer, Harald; Mora, Asier Urruela; Jones, Peter; Kirkbride, James; Rujescu, Dan; Tarricone, Ilaria; Borgwardt, Stefan; Harrisberger, Fabienne; Fm, Leweke; Seri, Marco; Marcacci, Thomas; Ittig, Sarah; European Network of National Networks studying Gene Environment Interactions in Schizophrenia (EU GEI) (van Os, J.; Storbini, Viviana; García Bernardo, Enrique; Minenna, Maria Gabriella; Ec, Atbaşoğlu; Hilboll, Desiree; La Barbera, Daniele; Cherny, Stacey S.; La Cascia, Caterina Erika; Chen, Eric Y. H.; Diaz Mesa, Eva; Mulè, Alice; Campbell, Desmond D.; Sideli, Lucia; Cirión, Aitziber Emaldi; Eş, Cankurtaran; Tripoli, Giada; Seminerio, Fabio; Cannon, Mary; Marinaro, Anna Maria; Berardi, Domenico; McGorry, Patrick; Bonora, Elena; Nelson, Barnaby; European Network authors, O. A.; Pantelis, Christos; Chiri, Luigi; Menezes, Paulo R.; Chierzi, Federico; Em, Díaz Mesa; Tenan, Silvia H. Gallo; Braca, Mauro; Shuhama, Rosana; Donegani, Ivonne; Ruggeri, Mirella; Fioritti, Angelo; Tosato, Sarah; Lasalvia, Antonio; Gei, European Network of National Networks studying Gene Environment Interactions in Schizophrenia (EU; Nordentoft, Merete; Ferraro, Laura; Krebs, Marie-Odile; Emaldi Cirión, Aitziber; Ey, Chen; Kwapil, Thomas R.; Amminger, G. Paul; Bp, Rutten; Del Ben, Cristina M.; Gp, Amminger; Maric, Nadja P.; Gallo Tenan, Silvia H.; Mihaljevic, Marina; Atbasoglu, E. Cem; Mirjanic, Tijana; Bernardo, Miguel; Ira, Elisa; Bonetto, Chiara; Cem Atbaşoğlu, E.; Am, Galliot; Am, Tronche; Barrantes-Vidal, Neus; Cristóbal, Paula; Dd, Campbell; Cm, Romeo Casabona; Brietzke, Elisa; Gadelha, Ary; Bressan, Rodrigo A.; Ce, La Cascia; Am, Marinaro; Cm, Del Ben; Andric, Sanja; Brietzk, Elisa

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Ulrich Reininghaus
ŞahinCankurtaran et al., 2014

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@article{ŞahinCankurtaran2014,
  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.},
  author = {ŞahinCankurtaran, Eylem and van der Gaa, Mark and van Os, Jim and Rutten, Bart P. and Van Os, J. and van Zelst, Catherine and Viechtbauer, Wolfgang and van der Ven, Elsje and Myin-Germeys, Inez and Van Zelst, C. and van der Meer, Floor and de Haan, Lieuwe and Reininghaus, Ulrich and van Dam, Daniella and Morgan, Craig and van Winkel, Ruud and Murray, Robin M. and O’Donovan, Michael C. and McGuire, Philip and Valmaggia, Lucia R. and Kempton, Matthew J. and Sartorio, Crocettarachele and Ucok, Alp and Stilo, Simona A. and Onyejiaka, Adanna and Modinos, Gemma and Karadag, Hasan and Tognin, Stefania and Sartorio, R. and O'Donovan, Michael C. and Rm, Murray and Owen, Michael J. and Sartorio, Rachele and Williams, Nigel and Paul Amminger, G. and Richards, Alexander and Pm, Llorca and Delespaul, Philippe and Meyer-Lindenberg, Andreas and Mc, O'Donovan and Leweke, F. Markus and Mj, Owen and Bruggeman, Richard and Tost, Heike and Luis Santos, Jose and Rohleder, Cathrin and Rodriguez Solano, Jose Juan and Lr, Valmaggia and Di Forti, Marta and Schwarz, Emanuel and Jm, Bumb and Üçok, Alp and Mj, Kempton and Saka, Meram Can and Gayer-Anderson, Charlotte and Mc, Saka and Hubbard, Kathryn and T.), Mirjanic and Pc, Sham and Beards, Stephanie and Sa, Stilo and Karadağ, Hasan and Soygür, Haldan and Ss, Cherny and Ulusoy, Semra and Bourque, Francois and Sanchez, Teresa and Sanchez, Emilio and Calem, Maria and Noyan, Handan and Karadayı, Gülşah and Jl, Santos and Ulaş, Halis and Jj, Rodríguez Solano and Holmans, Peter and Parellada, Mara and Craddock, Nicholas and Sanjuán, Julio and Humphreys, Isla and Schurhoff, Franck and Santos, Jose Luis and López, Gonzalo and Solano, José Juan Rodríguez and Akdeniz, Ceren and Roldán, Laura and Lopez, Gonzalo and Bumb, J. Malte and Alptekin, Köksal and Mesa, Eva Mª Díaz and Ms, Olmeda and Pouso, María and Markus Leweke, F. and Gülöksüz, Sinan and Jp, Selten and Gumus-Akay, Guvem and Atbagoǧlu, E. C. and Sánchez, Teresa and Rapado, Marta and Cihan, Burçin and Pr, Menezes and Martínez, Covadonga and Sánchez, Emilio and Sh, Gallo Tenan and Cankurtaran, Eylem Sahin and Velthorst, Eva and Olmeda, Mª Soledad and Akdede, Berna and Malte Bumb, J. and Binbay, Tolga and Ayer, Ahmet and Van Der Gaag, M. and Jr, Richard and Selten, Jean-Paul and Van Dam, D. and Akturan, Elçin and Van Der Ven, E. and Tr, Kwapil and Van Der Meer, F. and Arango, Celso and Messchaert, Elles and Ra, Bressan and Bernardo, M. and Kraan, Tamar and Nc, Stefanis and Bobes, Julio and Leboyer, Marion and Urruela Mora, Asier and Arrojo, Manuel and Szoke, Andrei and Schürhoff, Franck and Cuadrado, Pedro and Maria Romeo-Casabona, Carlos and Llorca, Pierre-Michel and Carracedo, Angel and Vilain, Jeanne and Bernardo, Enrique García and Tortelli, Andrea and Mg, Minenna and Cabrera, Bibiana and Cruz, Sabrina and Jiménez, Estela and Richard, Jean-Romain and González, Emiliano and Mo, Krebs and Tronche, Anne-Marie and Van Winkel, R. and De Haan, L. and Np, Maric and Thiery, Evert and Stefanis, Nikos C. and Nc Docks, at The University of North Carolina at Greensboro and Sachs, Gabriele and Winklbaur, Bernadette and Natl, European Network and Lasser, Iris and Burger, Nadine and Others,  and Schlögelhofer, Monika and Walter, Anna and Riecher-Rössler, Anita and Jamain, Stéphane and Frijda, Flora and Smieskova, Renata and Galliot, Anne-Marie and Rapp, Charlotte and Baudin, Grégoire and Ferchiou, Aziz and Soguel-Dit-Piquard, Fabienne and Bulzacka, Ewa and Studerus, Erich and Klosterkötter, Joachim and Charpeaud, Thomas and Ruhrmann, Stephan and De Hert, Marc and Paruch, Julia and Julkowski, Dominika and Decoster, Jeroen and Sham, Pak C. and Derom, Catherine and Guloksuz, Sinan and Li, Miaoxin and Romeo-Casabona, Carlos María and Gei), European Network of National Networks studying Gene Environment Interactions in Schizophrenia (EU and Aschauer, Harald and Mora, Asier Urruela and Jones, Peter and Kirkbride, James and Rujescu, Dan and Tarricone, Ilaria and Borgwardt, Stefan and Harrisberger, Fabienne and Fm, Leweke and Seri, Marco and Marcacci, Thomas and Ittig, Sarah and European Network of National Networks studying Gene Environment Interactions in Schizophrenia (EU GEI) (van Os, J. and Storbini, Viviana and García Bernardo, Enrique and Minenna, Maria Gabriella and Ec, Atbaşoğlu and Hilboll, Desiree and La Barbera, Daniele and Cherny, Stacey S. and La Cascia, Caterina Erika and Chen, Eric Y. H. and Diaz Mesa, Eva and Mulè, Alice and Campbell, Desmond D. and Sideli, Lucia and Cirión, Aitziber Emaldi and Eş, Cankurtaran and Tripoli, Giada and Seminerio, Fabio and Cannon, Mary and Marinaro, Anna Maria and Berardi, Domenico and McGorry, Patrick and Bonora, Elena and Nelson, Barnaby and European Network authors, O. A. and Pantelis, Christos and Chiri, Luigi and Menezes, Paulo R. and Chierzi, Federico and Em, Díaz Mesa and Tenan, Silvia H. Gallo and Braca, Mauro and Shuhama, Rosana and Donegani, Ivonne and Ruggeri, Mirella and Fioritti, Angelo and Tosato, Sarah and Lasalvia, Antonio and Gei, European Network of National Networks studying Gene Environment Interactions in Schizophrenia (EU and Nordentoft, Merete and Ferraro, Laura and Krebs, Marie-Odile and Emaldi Cirión, Aitziber and Ey, Chen and Kwapil, Thomas R. and Amminger, G. Paul and Bp, Rutten and Del Ben, Cristina M. and Gp, Amminger and Maric, Nadja P. and Gallo Tenan, Silvia H. and Mihaljevic, Marina and Atbasoglu, E. Cem and Mirjanic, Tijana and Bernardo, Miguel and Ira, Elisa and Bonetto, Chiara and Cem Atbaşoğlu, E. and Am, Galliot and Am, Tronche and Barrantes-Vidal, Neus and Cristóbal, Paula and Dd, Campbell and Cm, Romeo Casabona and Brietzke, Elisa and Gadelha, Ary and Bressan, Rodrigo A. and Ce, La Cascia and Am, Marinaro and Cm, Del Ben and Andric, Sanja and Brietzk, Elisa},
  doi = {10.1093/schbul/sbu069},
  month = {jan},
  title = {Identifying Gene-Environment Interactions in Schizophrenia: Contemporary Challenges for Integrated, Large-scale Investigations},
  url = {https://academic.oup.com/schizophreniabulletin/article-pdf/40/4/729/9349341/sbu069.pdf},
  year = {2014}
}

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Identifying Gene-Environment Interactions in Schizophrenia: Contemporary Challenges for Integrated, Large-scale Investigations

Journal article published in 2014 by Eylem ŞahinCankurtaran, Mark van der Gaa, Jim van Os, Bart P. Rutten, J. Van Os, Catherine van Zelst, Wolfgang Viechtbauer, Elsje van der Ven, Inez Myin-Germeys, C. Van Zelst, Floor van der Meer, Lieuwe de Haan, Ulrich Reininghaus

, Daniella van Dam, Craig Morgan and other authors. Eylem ŞahinCankurtaran, Mark van der Gaa, Jim van Os, Bart P. Rutten, J. Van Os, Catherine van Zelst, Wolfgang Viechtbauer, Elsje van der Ven, Inez Myin-Germeys, C. Van Zelst, Floor van der Meer, Lieuwe de Haan, Ulrich Reininghaus

, Daniella van Dam, Craig Morgan, Ruud van Winkel, Robin M. Murray, Michael C. O’Donovan, Philip McGuire, Lucia R. Valmaggia, Matthew J. Kempton

, Crocettarachele Sartorio, Alp Ucok, Simona A. Stilo, Adanna Onyejiaka, Gemma Modinos

, Hasan Karadag, Stefania Tognin, R. Sartorio, Michael C. O'Donovan, Murray Rm, Michael J. Owen, Rachele Sartorio, Nigel Williams, G. Paul Amminger, Alexander Richards, Llorca Pm, Philippe Delespaul

, Andreas Meyer-Lindenberg, O'Donovan Mc, F. Markus Leweke, Owen Mj, Richard Bruggeman, Heike Tost, Jose Luis Santos, Cathrin Rohleder, Jose Juan Rodriguez Solano, Valmaggia Lr, Marta Di Forti

, Emanuel Schwarz, Bumb Jm, Alp Üçok, Kempton Mj, Meram Can Saka, Charlotte Gayer-Anderson, Saka Mc, Kathryn Hubbard, Mirjanic T.), Sham Pc, Stephanie Beards, Stilo Sa, Hasan Karadağ, Haldan Soygür, Cherny Ss, Semra Ulusoy, Francois Bourque, Teresa Sanchez, Emilio Sanchez, Maria Calem, Handan Noyan, Gülşah Karadayı, Santos Jl, Halis Ulaş, Rodríguez Solano Jj, Peter Holmans, Mara Parellada

, Nicholas Craddock, Julio Sanjuán, Isla Humphreys, Franck Schurhoff, Jose Luis Santos, Gonzalo López, José Juan Rodríguez Solano, Ceren Akdeniz, Laura Roldán, Gonzalo Lopez, J. Malte Bumb, Köksal Alptekin, Eva Mª Díaz Mesa, Olmeda Ms, María Pouso, F. Markus Leweke, Sinan Gülöksüz

, Selten Jp, Guvem Gumus-Akay, E. C. Atbagoǧlu, Teresa Sánchez, Marta Rapado, Burçin Cihan, Menezes Pr, Covadonga Martínez, Emilio Sánchez, Gallo Tenan Sh, Eylem Sahin Cankurtaran, Eva Velthorst

, Mª Soledad Olmeda, Berna Akdede, J. Malte Bumb, Tolga Binbay

, Ahmet Ayer, M. Van Der Gaag

, Richard Jr, Jean-Paul Selten, D. Van Dam, Elçin Akturan, E. Van Der Ven, Kwapil Tr, F. Van Der Meer, Celso Arango, Elles Messchaert, Bressan Ra, M. Bernardo, Tamar Kraan, Stefanis Nc, Julio Bobes, Marion Leboyer, Asier Urruela Mora, Manuel Arrojo, Andrei Szoke, Franck Schürhoff, Pedro Cuadrado, Carlos Maria Romeo-Casabona, Pierre-Michel Llorca, Angel Carracedo, Jeanne Vilain, Enrique García Bernardo, Andrea Tortelli, Minenna Mg, Bibiana Cabrera, Sabrina Cruz, Estela Jiménez

, Jean-Romain Richard, Emiliano González, Krebs Mo, Anne-Marie Tronche, R. Van Winkel, L. De Haan, Maric Np, Evert Thiery, Nikos C. Stefanis, at The University of North Carolina at Greensboro Nc Docks, Gabriele Sachs, Bernadette Winklbaur, European Network Natl, Iris Lasser, Nadine Burger, Others, Monika Schlögelhofer, Anna Walter, Anita Riecher-Rössler, Stéphane Jamain, Flora Frijda, Renata Smieskova, Anne-Marie Galliot, Charlotte Rapp, Grégoire Baudin, Aziz Ferchiou, Fabienne Soguel-Dit-Piquard, Ewa Bulzacka, Erich Studerus, Joachim Klosterkötter, Thomas Charpeaud, Stephan Ruhrmann

, Marc De Hert, Julia Paruch, Dominika Julkowski, Jeroen Decoster, Pak C. Sham, Catherine Derom, Sinan Guloksuz, Miaoxin Li, Carlos María Romeo-Casabona, European Network of National Networks studying Gene Environment Interactions in Schizophrenia (EU Gei), Harald Aschauer, Asier Urruela Mora, Peter Jones, James Kirkbride, Dan Rujescu, Ilaria Tarricone, Stefan Borgwardt, Fabienne Harrisberger, Leweke Fm, Marco Seri, Thomas Marcacci, Sarah Ittig, J. European Network of National Networks studying Gene Environment Interactions in Schizophrenia (EU GEI) (van Os, Viviana Storbini, Enrique García Bernardo, Maria Gabriella Minenna, Atbaşoğlu Ec, Desiree Hilboll, Daniele La Barbera, Stacey S. Cherny, Caterina Erika La Cascia, Eric Y. H. Chen, Eva Diaz Mesa, Alice Mulè, Desmond D. Campbell, Lucia Sideli, Aitziber Emaldi Cirión, Cankurtaran Eş, Giada Tripoli, Fabio Seminerio, Mary Cannon

, Anna Maria Marinaro, Domenico Berardi, Patrick McGorry

, Elena Bonora, Barnaby Nelson

, O. A. European Network authors, Christos Pantelis, Luigi Chiri, Paulo R. Menezes, Federico Chierzi, Díaz Mesa Em, Silvia H. Gallo Tenan, Mauro Braca, Rosana Shuhama, Ivonne Donegani, Mirella Ruggeri, Angelo Fioritti, Sarah Tosato, Antonio Lasalvia, European Network of National Networks studying Gene Environment Interactions in Schizophrenia (EU Gei, Merete Nordentoft, Laura Ferraro, Marie-Odile Krebs, Aitziber Emaldi Cirión, Chen Ey, Thomas R. Kwapil, G. Paul Amminger

, Rutten Bp, Cristina M. Del Ben, Amminger Gp, Nadja P. Maric, Silvia H. Gallo Tenan, Marina Mihaljevic, E. Cem Atbasoglu, Tijana Mirjanic, Miguel Bernardo, Elisa Ira, Chiara Bonetto, E. Cem Atbaşoğlu, Galliot Am, Tronche Am, Neus Barrantes-Vidal

, Paula Cristóbal, Campbell Dd, Romeo Casabona Cm, Elisa Brietzke, Ary Gadelha, Rodrigo A. Bressan, La Cascia Ce, Marinaro Am, Del Ben Cm, Sanja Andric, Elisa Brietzk

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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 × 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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Identifying Gene-Environment Interactions in Schizophrenia: Contemporary Challenges for Integrated, Large-scale Investigations

Abstract