title: Is NOTCH4 associated with schizophrenia?
abstract: The NOTCH4 locus was reported to be associated with schizophrenia in our previous study but the subsequent replication by other workers has been inconsistent. To find out possible reasons for the poor replication, the present work was undertaken to analyse four functional single nucleotide polymorphisms (SNPs) (rs367398, rs915894, rs520692 and rs422951) at the NOTCH4 locus among 141 schizophrenic family trios of Chinese Han descent. Of these four SNPs, rs520692 was the only one associated with schizophrenia (P = 0.017); the other three, however, did not show any association with the illness, including rs367398 located in the promoter region, which had shown a strong association with the illness in our previous study conducted with British samples. Although these four SNPs analysed lie within a less than 4 kb segment of genomic DNA, the pattern of linkage disequilibrium between them was unexpected. The strongest linkage disequilibrium was shown only between rs367398 and rs520692 and between rs520692 and rs422951 in both parent and patient groups. This study raises the possibility that there might be two or more disease-underlying variants at the NOTCH4 locus or at a nearby locus, and that the allelic or locus heterogeneity may be one of the possible reasons for the poor replication of the NOTCH4 finding.
authors.affiliation: Jilin University Research Center for Genomic Medicine, National Center of Human Genome Research, Changchun, Jilin, China.
authors.forename: Xuan
authors.initials: X
authors.lastname: Zhang
authors.forename: Jun
authors.initials: J
authors.lastname: Wei
authors.forename: Ya-Qin
authors.initials: YQ
authors.lastname: Yu
authors.forename: Shu-Zheng
authors.initials: SZ
authors.lastname: Liu
authors.forename: Jie-Ping
authors.initials: JP
authors.lastname: Shi
authors.forename: Lin-Lin
authors.initials: LL
authors.lastname: Liu
authors.forename: Gui-Zhi
authors.initials: GZ
authors.lastname: Ju
authors.forename: Jian-Zhong
authors.initials: JZ
authors.lastname: Yang
authors.forename: Dai
authors.initials: D
authors.lastname: Zhang
authors.forename: Qi
authors.initials: Q
authors.lastname: Xu
authors.forename: Yan
authors.initials: Y
authors.lastname: Shen
authors.forename: Gwynneth P
authors.initials: GP
authors.lastname: Hemmings
mesh_terms: D000328:Adult; D044466:Asian People / Q000235:genetics; D002681:China / Q000453:epidemiology; D005091:Exons / Q000235:genetics; D005260:Female; D018740:Genetic Heterogeneity; D020022:Genetic Predisposition to Disease; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D000074562:Receptor, Notch4; D011956:Receptors, Cell Surface / Q000235:genetics*; D051880:Receptors, Notch; D012559:Schizophrenia / Q000208:ethnology / Q000235:genetics*
chemical_list: C106075:NOTCH4 protein, human; D011518:Proto-Oncogene Proteins; D000074562:Receptor, Notch4; D011956:Receptors, Cell Surface; D051880:Receptors, Notch