title: NOTCH4 gene haplotype is associated with schizophrenia in African Americans.
abstract: BACKGROUND
  The goal of this study was to investigate the relationship between the NOTCH4 gene and schizophrenia in African American (AA) and European American (EA) subjects.
  
  
  METHODS
  Two single nucleotide polymorphisms (SNPs) at the NOTCH4 locus were genotyped in 123 AA schizophrenia patients, 223 EA schizophrenia patients, 85 AA healthy control subjects, and 211 EA healthy control subjects. The specific markers studied were -1725T/G and -25T/C. Comparisons of allele and haplotype frequencies between patients and control subjects were performed with the chi-square test, the Fisher's Exact Test, and CLUMP software. Linkage disequilibrium (LD) between these two SNPs was calculated with the 3LOCUS program.
  
  
  RESULTS
  The haplotype -1725G/-25T associates to schizophrenia in AA subjects (p =.0008), but not in EA subjects. Alleles -1725G and allele -25T are in positive LD both in AAs and EAs. Allele and haplotype frequencies differ significantly between AAs and EAs.
  
  
  CONCLUSIONS
  The haplotype -1725G/-25T at the NOTCH4 locus, which results from SNPs of NOTCH4 that are in LD, may increase susceptibility to schizophrenia in AAs. Any effect of this locus on risk for schizophrenia is population-specific.
authors.affiliation: Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut, USA.
authors.forename: Xingguang
authors.initials: X
authors.lastname: Luo
authors.forename: Tim A
authors.initials: TA
authors.lastname: Klempan
authors.forename: Jaakko
authors.initials: J
authors.lastname: Lappalainen
authors.forename: Robert A
authors.initials: RA
authors.lastname: Rosenheck
authors.forename: Dennis S
authors.initials: DS
authors.lastname: Charney
authors.forename: Joseph
authors.initials: J
authors.lastname: Erdos
authors.forename: Daniel P
authors.initials: DP
authors.lastname: van Kammen
authors.forename: Henry R
authors.initials: HR
authors.lastname: Kranzler
authors.forename: James L
authors.initials: JL
authors.lastname: Kennedy
authors.forename: Joel
authors.initials: J
authors.lastname: Gelernter
mesh_terms: D001741:Black or African American / Q000235:genetics*; D000483:Alleles; D016009:Chi-Square Distribution; D003545:Cysteine / Q000235:genetics; D039721:Diagnostic and Statistical Manual of Mental Disorders; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D005838:Genotype; D005998:Glycine / Q000235:genetics; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D016133:Polymerase Chain Reaction / Q000379:methods; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D000074562:Receptor, Notch4; D011956:Receptors, Cell Surface; D051880:Receptors, Notch; D012559:Schizophrenia / Q000208:ethnology / Q000235:genetics*; D013912:Threonine / Q000235:genetics
chemical_list: C106075:NOTCH4 protein, human; D011518:Proto-Oncogene Proteins; D000074562:Receptor, Notch4; D011956:Receptors, Cell Surface; D051880:Receptors, Notch; D013912:Threonine; D003545:Cysteine; D005998:Glycine