An update on the genetics of schizophrenia.
OBJECTIVE
This paper reviews recent molecular genetic studies of schizophrenia and evaluates claims implicating specific genes as susceptibility loci.


RESULTS
Molecular genetic studies have identified several potential regions of linkage and two associated chromosomal abnormalities, and the evidence is accumulating in favour of several positional candidate genes. Currently, the strongest evidence for putative schizophrenia susceptibility loci relates to the genes encoding dysbindin (DTNBP1) and neuregulin (NRG1). For other genes, disrupted in schizophrenia (DISC1), D-amino acid oxidase activator (DAOA), regulator of G-protein signalling 4 (RGS4) and V-AKT murine thymoma viral oncogene homolog 1 (AKT1) the data are promising but not yet compelling. In the most convincing cases, the risk haplotypes appear to be associated with small effect sizes and do not fully explain the linkage findings that prompted each study.


CONCLUSIONS
The ability of positional genetics to implicate novel genes and pathways will open up new vistas for neurobiological research. Despite the accumulation of significant genetic data, however, the susceptibility variants have yet to be identified and detailed follow-up studies are now required.
Norton
Nadine
N
Department of Psychological Medicine, Wales School of Medicine, Cardiff University, Heath Park, Cardiff, UK. Nortonn@cf.ac.uk
Williams
Hywel J
HJ
Owen
Michael J
MJ
D000483:Alleles; D002352:Carrier Proteins / Q000235:genetics; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics; D003605:D-Amino-Acid Oxidase / Q000235:genetics; D000074765:Dysbindin; D049029:Dystrophin-Associated Proteins; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008967:Molecular Biology / Q000379:methods*; D009419:Nerve Tissue Proteins / Q000235:genetics; D020890:Neuregulin-1; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics; D020710:RGS Proteins / Q000235:genetics; D012559:Schizophrenia / Q000235:genetics*
D002352:Carrier Proteins; C475071:DAOA protein, human; C432416:DTNBP1 protein, human; D000074765:Dysbindin; D049029:Dystrophin-Associated Proteins; D047908:Intracellular Signaling Peptides and Proteins; C094131:NRG1 protein, human; D009419:Nerve Tissue Proteins; D020890:Neuregulin-1; D020710:RGS Proteins; C098799:RGS4 protein; C417983:DAO protein, human; D003605:D-Amino-Acid Oxidase; C494918:AKT1 protein, human; D051057:Proto-Oncogene Proteins c-akt