TY - JOUR
T1 - Genome-Wide Findings in Schizophrenia and the Role of Gene-Environment Interplay
AU - van Winkel, Ruud
AU - Esquivel, Gabriel
AU - Kenis, Gunter
AU - Wichers, Marieke
AU - Collip, Dina
AU - Peerbooms, Odette
AU - Rutten, Bart
AU - Myin-Germeys, Inez
AU - van Os, Jim
PY - 2010
Y1 - 2010
N2 - 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.
AB - 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.
KW - Cannabis
KW - Gene-environment interaction
KW - GWAS
KW - Psychosis
KW - Trauma
U2 - 10.1111/j.1755-5949.2010.00155.x
DO - 10.1111/j.1755-5949.2010.00155.x
M3 - Article
C2 - 20553308
SN - 1755-5930
VL - 16
SP - e185-e192
JO - CNS Neuroscience & Therapeutics
JF - CNS Neuroscience & Therapeutics
IS - 5
ER -