REVIEW: Genome-wide findings in schizophrenia and the role of gene-environment interplay.
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.
Van Winkel
Ruud
R
Department of Psychiatry and Neuropsychology, EURON, Maastricht University Medical Centre, The Netherlands. ruud.vanwinkel@sp.unimaas.nl
Esquivel
Gabriel
G
Kenis
Gunter
G
Wichers
Marieke
M
Collip
Dina
D
Peerbooms
Odette
O
Rutten
Bart
B
Myin-Germeys
Inez
I
Van Os
Jim
J
D004777:Environment; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study / Q000379:methods*; D006801:Humans; D008957:Models, Genetic; D012559:Schizophrenia / Q000235:genetics*