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 Bourque; Gemma 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 Atbaşoğlu; Sinan Gülöksüz; Guvem Gumus-Akay; Burçin Cihan; Hasan Karadağ; Haldan Soygür; Eylem Şahin Cankurtaran; Semra Ulusoy; Berna Akdede; Merete Nordentoft; European Network of National Networks studying Gene-Environment Interactions in Schizophrenia (EU-GEI)

doi:10.1093/schbul/sbu069

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 Atbaşoğlu, Sinan Gülöksüz, Guvem Gumus-Akay, Burçin Cihan, Hasan Karadağ, Haldan Soygür, Eylem Şahin Cankurtaran, Semra Ulusoy, Berna Akdede, Merete Nordentoft, European Network of National Networks studying Gene-Environment Interactions in Schizophrenia (EU-GEI)

Department of Clinical Medicine

156 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.

Original language	English
Journal	Schizophrenia Bulletin
Volume	40
Issue number	4
Pages (from-to)	729-736
Number of pages	8
ISSN	0586-7614
DOIs	https://doi.org/10.1093/schbul/sbu069
Publication status	Published - Jul 2014

Keywords

Gene-Environment Interaction
Genetic Predisposition to Disease
Humans
Schizophrenia
Schizophrenic Psychology
Social Environment

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10.1093/schbul/sbu069

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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., ... European Network of National Networks studying Gene-Environment Interactions in Schizophrenia (EU-GEI) (2014). Identifying Gene-Environment Interactions in Schizophrenia: Contemporary Challenges for Integrated, Large-scale Investigations. Schizophrenia Bulletin, 40(4), 729-736. https://doi.org/10.1093/schbul/sbu069

van Os, J, Rutten, BP, Myin-Germeys, I, Delespaul, P, Viechtbauer, W, van Zelst, C, Bruggeman, R, Reininghaus, U, Morgan, C, Murray, RM, Di Forti, M, McGuire, P, Valmaggia, LR, Kempton, MJ, Gayer-Anderson, C, Hubbard, K, Beards, S, Stilo, SA, Onyejiaka, A, Bourque, F, Modinos, G, Tognin, S, Calem, M, O'Donovan, MC, Owen, MJ, Holmans, P, Williams, N, Craddock, N, Richards, A, Humphreys, I, Meyer-Lindenberg, A, Leweke, FM, Tost, H, Akdeniz, C, Rohleder, C, Bumb, JM, Schwarz, E, Alptekin, K, Üçok, A, Saka, MC, Atbaşoğlu, EC, Gülöksüz, S, Gumus-Akay, G, Cihan, B, Karadağ, H, Soygür, H, Cankurtaran, EŞ, Ulusoy, S, Akdede, B, Nordentoft, M & European Network of National Networks studying Gene-Environment Interactions in Schizophrenia (EU-GEI) 2014, 'Identifying Gene-Environment Interactions in Schizophrenia: Contemporary Challenges for Integrated, Large-scale Investigations', Schizophrenia Bulletin, vol. 40, no. 4, pp. 729-736. https://doi.org/10.1093/schbul/sbu069

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

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.",

keywords = "Gene-Environment Interaction, Genetic Predisposition to Disease, Humans, Schizophrenia, Schizophrenic Psychology, Social Environment",

author = "{van Os}, Jim and Rutten, {Bart P} and Inez Myin-Germeys and Philippe Delespaul and Wolfgang Viechtbauer and {van Zelst}, Catherine and Richard Bruggeman and Ulrich Reininghaus and Craig Morgan and Murray, {Robin M} and {Di Forti}, Marta and Philip McGuire and Valmaggia, {Lucia R} and Kempton, {Matthew J} and Charlotte Gayer-Anderson and Kathryn Hubbard and Stephanie Beards and Stilo, {Simona A} and Adanna Onyejiaka and Francois Bourque and Gemma Modinos and Stefania Tognin and Maria Calem and O'Donovan, {Michael C} and Owen, {Michael J} and Peter Holmans and Nigel Williams and Nicholas Craddock and Alexander Richards and Isla Humphreys and Andreas Meyer-Lindenberg and Leweke, {F Markus} and Heike Tost and Ceren Akdeniz and Cathrin Rohleder and Bumb, {J Malte} and Emanuel Schwarz and K{\"o}ksal Alptekin and Alp {\"U}{\c c}ok and Saka, {Meram Can} and Atba{\c s}oğlu, {E Cem} and Sinan G{\"u}l{\"o}ks{\"u}z and Guvem Gumus-Akay and Bur{\c c}in Cihan and Hasan Karadağ and Haldan Soyg{\"u}r and Cankurtaran, {Eylem {\c S}ahin} and Semra Ulusoy and Berna Akdede and Merete Nordentoft and {European Network of National Networks studying Gene-Environment Interactions in Schizophrenia (EU-GEI)}",

note = "{\textcopyright} The Author 2014. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: [email protected].",

year = "2014",

month = jul,

doi = "10.1093/schbul/sbu069",

language = "English",

volume = "40",

pages = "729--736",

journal = "Schizophrenia Bulletin",

issn = "0586-7614",

publisher = "Oxford University Press",

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T1 - Identifying Gene-Environment Interactions in Schizophrenia

T2 - Contemporary Challenges for Integrated, Large-scale Investigations

AU - van Os, Jim

AU - Rutten, Bart P

AU - Myin-Germeys, Inez

AU - Delespaul, Philippe

AU - Viechtbauer, Wolfgang

AU - van Zelst, Catherine

AU - Bruggeman, Richard

AU - Reininghaus, Ulrich

AU - Morgan, Craig

AU - Murray, Robin M

AU - Di Forti, Marta

AU - McGuire, Philip

AU - Valmaggia, Lucia R

AU - Kempton, Matthew J

AU - Gayer-Anderson, Charlotte

AU - Hubbard, Kathryn

AU - Beards, Stephanie

AU - Stilo, Simona A

AU - Onyejiaka, Adanna

AU - Bourque, Francois

AU - Modinos, Gemma

AU - Tognin, Stefania

AU - Calem, Maria

AU - O'Donovan, Michael C

AU - Owen, Michael J

AU - Holmans, Peter

AU - Williams, Nigel

AU - Craddock, Nicholas

AU - Richards, Alexander

AU - Humphreys, Isla

AU - Meyer-Lindenberg, Andreas

AU - Leweke, F Markus

AU - Tost, Heike

AU - Akdeniz, Ceren

AU - Rohleder, Cathrin

AU - Bumb, J Malte

AU - Schwarz, Emanuel

AU - Alptekin, Köksal

AU - Üçok, Alp

AU - Saka, Meram Can

AU - Atbaşoğlu, E Cem

AU - Gülöksüz, Sinan

AU - Gumus-Akay, Guvem

AU - Cihan, Burçin

AU - Karadağ, Hasan

AU - Soygür, Haldan

AU - Cankurtaran, Eylem Şahin

AU - Ulusoy, Semra

AU - Akdede, Berna

AU - Nordentoft, Merete

AU - European Network of National Networks studying Gene-Environment Interactions in Schizophrenia (EU-GEI)

PY - 2014/7

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N2 - 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.

AB - 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.

KW - Gene-Environment Interaction

KW - Genetic Predisposition to Disease

KW - Humans

KW - Schizophrenia

KW - Schizophrenic Psychology

KW - Social Environment

U2 - 10.1093/schbul/sbu069

DO - 10.1093/schbul/sbu069

M3 - Journal article

C2 - 24860087

SN - 0586-7614

VL - 40

SP - 729

EP - 736

JO - Schizophrenia Bulletin

JF - Schizophrenia Bulletin

IS - 4

ER -

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

Abstract

Keywords

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