%0 Journal Article
%T A re-review of the association between the NOTCH4 locus and schizophrenia.
%A Shayevitz C
%A Cohen OS
%A Faraone SV
%A Glatt SJ
%J Am J Med Genet B Neuropsychiatr Genet
%V 159
%N 5
%D Jul 2012
%M 22488909
%F 3.358
%R 10.1002/ajmg.b.32050
%X NOTCH4 has long been identified as a candidate susceptibility gene for schizophrenia, but the collective body of genetic association studies of this gene has been less than conclusive. Recently a variant in NOTCH4 was implicated as one of the most reliably associated polymorphisms observed in a genome-wide association scan of the disorder, and the collective evidence for this polymorphism now surpasses criteria for genome-wide significance. To place these developments in context, we now summarize the initial work identifying NOTCH4 as a candidate gene for schizophrenia. The results of the genome-wide association studies that have confirmed this as a risk gene, and novel bioinformatics analyses that reveal potential functional profiles of the most likely risk-conferring polymorphisms. These analyses suggest that the NOTCH4 polymorphisms most strongly associated with schizophrenia exert their effects on susceptibility by altering the efficiency and/or alternative splicing of Notch4 transcripts. Further experimental evidence should be pursued to clarify the NOTCH4-regulated molecular and cellular phenotypes of relevance to the disorder, and the functional consequences of the implicated polymorphisms in the gene.