Schizophrenia genetics: advancing on two fronts

Recent studies have supported the hypothesis that the high heritability of schizophrenia reflects a combination of relatively common alleles of small effect and some rare alleles with relatively large effects. Genome-wide association studies have identified at least one common allele of small effect at ZNF804a, which encodes a putative zinc finger binding protein, as well as possible roles for other loci. The genome-wide studies of at least one class of relatively uncommon variant, submicroscopic chromosomal abnormalities often referred to as copy number variations (CNVs), suggest that these confer high risk of schizophrenia. There is evidence both for an increased burden of CNVs in schizophrenia and that risk is conferred by specific large deletions at 1q21.1 and at 15q13.2 and by deletions of NRXN1 which encodes the synaptic scaffolding protein neurexin 1.