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A re‐review of the association between the NOTCH4 locus and schizophrenia
Author(s) -
Shayevitz Christina,
Cohen Ori S.,
Faraone Stephen V.,
Glatt Stephen J.
Publication year - 2012
Publication title -
american journal of medical genetics part b: neuropsychiatric genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.393
H-Index - 126
eISSN - 1552-485X
pISSN - 1552-4841
DOI - 10.1002/ajmg.b.32050
Subject(s) - genetics , biology , candidate gene , genetic association , genome wide association study , locus (genetics) , gene , schizophrenia (object oriented programming) , context (archaeology) , single nucleotide polymorphism , genotype , medicine , psychiatry , paleontology
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. © 2012 Wiley Periodicals, Inc.