Maastricht Univ Kings Coll London Mondriaan Mental Hlth Trust Univ Groningen Cardiff Univ Cent Inst Mental Hlth Dokuz Eylul Univ Istanbul Univ Ankara Univ Yale Univ Middle E Tech Univ Diskapi YB Res & Training Hosp Turkish Federat Schizophrenia Assoc Ataturk Training & Res Hosp Manisa Mental Hlth Hosp Univ Complutense Univ Barcelona Univ Valencia Univ Oviedo Univ Santiago de Compostela Hosp Virgen de la Luz Hosp Univ Infanta Leonor Hosp Virgen Torre Hosp Clin Univ Hosp Psiquiatr Conxo Univ Amsterdam Vrije Univ Amsterdam EMGO Inst Hlth & Care Res Parnassia Psychiat Inst Rivierduinen Psychiat Inst Grp Hosp Mondor Hop Henri Mondor Univ Paris Est Fdn Fondamental CMP B CHU Univ Auvergne EPS Maison Blanche UPC KU Leuven UPC Katholieke Univ Leuven Assoc Sci Res Multiple Births Univ Ghent Univ Athens Med Univ Vienna Psychiat Univ Clin Basel Univ Cologne Univ Hong Kong Univ Basque Country Univ Zaragoza Univ Cambridge UCL Royal Coll Surgeons Ireland Univ Munich Univ Bologna Local Hlth Trust Univ Palermo P Giaccone Gen Hosp Univ Melbourne Universidade de São Paulo (USP) Univ Verona Copenhagen Univ Hosp Univ Paris 05 Univ Autonoma Barcelona St Pere Claver Fundacio Sanitaria Univ N Carolina CIBERSAM Universidade Federal de São Paulo (UNIFESP) Univ Belgrade
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.