Brief report| Volume 54, ISSUE 11, P1298-1301, December 01, 2003

Association study of the human FZD3 locus with schizophrenia



      The FZD3 protein is a transmembrane receptor for secreted Wnt glycoproteins involved in the Wnt signal transduction cascades. The alteration of Wnt signal transduction cascades has been thought to be involved in producing the cytoarchitectural defects observed in schizophrenia. Because the human FZD3 gene is mapped to chromosome 8p21, which is a potential region containing a gene for schizophrenia, it may play a role in conferring susceptibility to the disease.


      This study was conducted with the detection of three single nucleotide polymorphisms (SNPs) located within the FZD3 locus by using the polymerase chain reaction–based restriction fragment length polymorphism (RFLP) analysis among 246 schizophrenic family trios of Chinese Han descent.


      The transmission disequilibrium test (TDT) demonstrated that the three SNPs all showed a preferential transmission with a p value ranging from .0003–.000007. The global chi-squared test for haplotype transmission also showed a strong association (χ2 = 48.84, df = 7, p < .000001).


      The strong association between the FZD3 locus and schizophrenia suggests that the gene itself may play a role in underlying schizophrenia, although a nearby gene responsible for predisposing to the illness cannot be ruled out.


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Biological Psychiatry
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Arnold S.E.
        Neurodevelopmental abnormalities in schizophrenia.
        Dev Psychopathol. 1999; 11: 439-456
        • Beasley C.
        • Cotter D.
        • Khan N.
        • Pollard C.
        • Sheppard P.
        • Varndell I.
        • et al.
        Glycogen synthase kinase-3beta immunoreactivity is reduced in the prefrontal cortex in schizophrenia.
        Neurosci Lett. 2001; 20: 117-120
        • Bloom F.E.
        Advancing a neurodevelopmental origin for schizophrenia.
        Arch Gen Psychiatry. 1993; 50: 224-227
        • Chiano M.N.
        • Clayton D.G.
        Fine genetic mapping using haplotype analysis and the missing data problem.
        Ann Human Genet. 1998; 62: 55-60
        • Cotter D.
        • Kerwin R.
        • al-Sarraji S.
        • Brion J.P.
        • Chadwich A.
        • Lovestone S.
        Abnormalities of Wnt signaling in schizophrenia—evidence for neurodevelopmental abnormality.
        NeuroReport. 1998; 9: 1379-1383
        • Hall A.C.
        • Lucas F.R.
        • Salinas P.C.
        Axonal remodeling and synaptic differentiation in the cerebellum is regulated by WNT-7a signaling.
        Cell. 2000; 100: 525-535
        • Kendler K.S.
        • MacLean C.J.
        • O’Neill F.A.
        • Burke J.
        • Murphy B.
        • Duke F.
        • et al.
        Evidence for a schizophrenia vulnerability locus on chromosome 8p in the Irish study of high-density schizophrenia Families.
        Am J Psychiatry. 1996; 153: 1534-1540
        • Lee K.J.
        • Jessell T.M.
        The specification of dorsal cell fates in the vertebrate central nervous system.
        Annu Rev Neurosci. 1999; 22: 261-294
        • Lieberman J.A.
        Is schizophrenia a neurodegenerative disorder? A clinical and neurobiological perspective.
        Biol Psychiatry. 1999; 15: 729-739
        • McMahon A.P.
        • Bradley A.
        The Wnt-1 (int-1) proto-oncogene is required for development of a large region of the mouse brain.
        Cell. 1991; 62: 1073-1085
        • Miyaoka T.
        • Seno H.
        • Ishino H.
        Increased expression of Wnt-1 in schizophrenic brains.
        Schizophr Res. 1999; 38: 1-6
        • Murry R.M.
        Neurodevelopmental schizophrenia.
        Br J Psychiatry. 1994; 165: 6-12
        • Patapoutian A.
        • Reichardt L.F.
        Roles of Wnt proteins in neural development and maintenance.
        Curr Opin Neurobiol. 2000; 10: 392-399
        • Pulver A.E.
        • Lasseter V.K.
        • Kasch L.
        • Wolyniec P.
        • Nestadt G.
        • Blouin J.L.
        • et al.
        Am J Med Genet. 1995; 60: 252-260
        • Pulver A.E.
        • Mulle J.
        • Swartz K.L.
        • Blouin J.-L.
        • Dombroski B.
        • Liang K.-Y.
        • et al.
        Genetic heterogeneity in schizophrenia.
        Mol Psychiatry. 2000; 5: 650-653
        • Sala C.F.
        • Formenti E.
        • Terstappen G.C.
        • Caricasole A.
        Identification, gene structure, and expression of human frizzled-3 (FZD3).
        Biochem Biophys Res Commun. 2000; 273: 27-34
        • Schizophrenia Linkage Group
        Additional support for schizophrenia linkage on chromosomes 6 and 8.
        Am J Med Genet. 1996; 67: 580-594
        • Sokol S.Y.
        Wnt signaling and dorso-ventral axis specification in vertebrates.
        Curr Opin Genet Dev. 1999; 9: 405-410
        • Spielman R.S.
        • McGinnis R.E.
        • Ewens W.J.
        Transmission tests for linkage disequilibrium.
        Am J Hum Genet. 1993; 52: 506-516
        • Wang Y.
        • Thekdi N.
        • Smallwood P.M.
        • Macke J.P.
        • Nathans J.
        Frizzled-3 is required for the development of major fiber tracts in the rostral CNS.
        J Neurosci. 2002; 22: 8563-8573
        • Weinberger D.R.
        Implications of normal brain development for the pathogenesis of schizophrenia.
        Arch Gen Psychiatry. 1987; 44: 660-669