title: REVIEW: Genome-wide findings in schizophrenia and the role of gene-environment interplay.
abstract: The recent advent of genome-wide mass-marker technology has resulted in renewed optimism to unravel the genetic architecture of psychotic disorders. Genome-wide association studies have identified a number of common polymorphisms robustly associated with schizophrenia, in ZNF804A, transcription factor 4, major histocompatibility complex, and neurogranin. In addition, copy number variants (CNVs) in 1q21.1, 2p16.3, 15q11.2, 15q13.3, 16p11.2, and 22q11.2 were convincingly implicated in schizophrenia risk. Furthermore, these studies have suggested considerable genetic overlap with bipolar disorder (particularly for common polymorphisms) and neurodevelopmental disorders such as autism (particularly for CNVs). The influence of these risk variants on relevant intermediate phenotypes needs further study. In addition, there is a need for etiological models of psychosis integrating genetic risk with environmental factors associated with the disorder, focusing specifically on environmental impact on gene expression (epigenetics) and convergence of genes and environment on common biological pathways bringing about larger effects than those of genes or environment in isolation (gene-environment interaction). Collaborative efforts that bring together expertise in statistics, genetics, epidemiology, experimental psychiatry, brain imaging, and clinical psychiatry will be required to succeed in this challenging task.
authors.affiliation: Department of Psychiatry and Neuropsychology, EURON, Maastricht University Medical Centre, The Netherlands. ruud.vanwinkel@sp.unimaas.nl
authors.forename: Ruud
authors.initials: R
authors.lastname: Van Winkel
authors.forename: Gabriel
authors.initials: G
authors.lastname: Esquivel
authors.forename: Gunter
authors.initials: G
authors.lastname: Kenis
authors.forename: Marieke
authors.initials: M
authors.lastname: Wichers
authors.forename: Dina
authors.initials: D
authors.lastname: Collip
authors.forename: Odette
authors.initials: O
authors.lastname: Peerbooms
authors.forename: Bart
authors.initials: B
authors.lastname: Rutten
authors.forename: Inez
authors.initials: I
authors.lastname: Myin-Germeys
authors.forename: Jim
authors.initials: J
authors.lastname: Van Os
mesh_terms: D004777:Environment; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study / Q000379:methods*; D006801:Humans; D008957:Models, Genetic; D012559:Schizophrenia / Q000235:genetics*