Positional pathway screen of wnt signaling genes in schizophrenia: association with DKK4

Petroula Proitsi, Tao Li, Gillian Hamilton, Marta Di Forti, David Collier, Richard Killick, Ronald Chen, Pak Sham, Robin Murray, John Powell, Simon Lovestone

Research output: Contribution to journalArticle

Abstract

BACKGROUND: Wnt signaling has been implicated in schizophrenia from studies of gene expression in patients, from an understanding of the function of reported susceptibility genes and from experimental studies of psychoactive drugs. This diverse evidence suggests that wnt signaling genes, defined as pathway participants, modifiers or targets, are good candidates as susceptibility factors. METHODS: We performed a combined positional and candidate association screen by identifying known wnt signaling genes in regions linked to schizophrenia. In a staged study we examined over 50 single nucleotide polymorphisms (SNPs) in 28 wnt signaling genes, first in trios of Chinese origin and then in a case-control series from Hong Kong. RESULTS: In both sets, Dickkopf 4 (DKK4) was associated with schizophrenia - with an odds ratio of 3.9 (p <.01, CI = 1.3-11.1) in the combined sample. CONCLUSIONS: As DKK family members have previously been found to show altered expression in schizophrenia brain and to bind to neuregulin, this finding suggests that DKK4 may play a role in schizophrenia pathogenesis.
Original languageEnglish
Pages (from-to)13-16
Number of pages4
JournalBiological Psychiatry
Volume63
Issue number1
DOIs
Publication statusPublished - 1 Jan 2008

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Wnt Signaling Pathway
Schizophrenia
Genes
Neuregulins
Psychotropic Drugs
Hong Kong
Single Nucleotide Polymorphism
Odds Ratio
Gene Expression
Brain

Keywords

  • association
  • Dickkopf
  • DKK
  • genetics
  • schizophrenia
  • wnt signalling

Cite this

Proitsi, Petroula ; Li, Tao ; Hamilton, Gillian ; Di Forti, Marta ; Collier, David ; Killick, Richard ; Chen, Ronald ; Sham, Pak ; Murray, Robin ; Powell, John ; Lovestone, Simon. / Positional pathway screen of wnt signaling genes in schizophrenia : association with DKK4. In: Biological Psychiatry. 2008 ; Vol. 63, No. 1. pp. 13-16.
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Proitsi, P, Li, T, Hamilton, G, Di Forti, M, Collier, D, Killick, R, Chen, R, Sham, P, Murray, R, Powell, J & Lovestone, S 2008, 'Positional pathway screen of wnt signaling genes in schizophrenia: association with DKK4', Biological Psychiatry, vol. 63, no. 1, pp. 13-16. https://doi.org/10.1016/j.biopsych.2007.03.014

Positional pathway screen of wnt signaling genes in schizophrenia : association with DKK4. / Proitsi, Petroula; Li, Tao; Hamilton, Gillian; Di Forti, Marta; Collier, David; Killick, Richard; Chen, Ronald; Sham, Pak; Murray, Robin; Powell, John; Lovestone, Simon.

In: Biological Psychiatry, Vol. 63, No. 1, 01.01.2008, p. 13-16.

Research output: Contribution to journalArticle

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T1 - Positional pathway screen of wnt signaling genes in schizophrenia

T2 - association with DKK4

AU - Proitsi, Petroula

AU - Li, Tao

AU - Hamilton, Gillian

AU - Di Forti, Marta

AU - Collier, David

AU - Killick, Richard

AU - Chen, Ronald

AU - Sham, Pak

AU - Murray, Robin

AU - Powell, John

AU - Lovestone, Simon

PY - 2008/1/1

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N2 - BACKGROUND: Wnt signaling has been implicated in schizophrenia from studies of gene expression in patients, from an understanding of the function of reported susceptibility genes and from experimental studies of psychoactive drugs. This diverse evidence suggests that wnt signaling genes, defined as pathway participants, modifiers or targets, are good candidates as susceptibility factors. METHODS: We performed a combined positional and candidate association screen by identifying known wnt signaling genes in regions linked to schizophrenia. In a staged study we examined over 50 single nucleotide polymorphisms (SNPs) in 28 wnt signaling genes, first in trios of Chinese origin and then in a case-control series from Hong Kong. RESULTS: In both sets, Dickkopf 4 (DKK4) was associated with schizophrenia - with an odds ratio of 3.9 (p <.01, CI = 1.3-11.1) in the combined sample. CONCLUSIONS: As DKK family members have previously been found to show altered expression in schizophrenia brain and to bind to neuregulin, this finding suggests that DKK4 may play a role in schizophrenia pathogenesis.

AB - BACKGROUND: Wnt signaling has been implicated in schizophrenia from studies of gene expression in patients, from an understanding of the function of reported susceptibility genes and from experimental studies of psychoactive drugs. This diverse evidence suggests that wnt signaling genes, defined as pathway participants, modifiers or targets, are good candidates as susceptibility factors. METHODS: We performed a combined positional and candidate association screen by identifying known wnt signaling genes in regions linked to schizophrenia. In a staged study we examined over 50 single nucleotide polymorphisms (SNPs) in 28 wnt signaling genes, first in trios of Chinese origin and then in a case-control series from Hong Kong. RESULTS: In both sets, Dickkopf 4 (DKK4) was associated with schizophrenia - with an odds ratio of 3.9 (p <.01, CI = 1.3-11.1) in the combined sample. CONCLUSIONS: As DKK family members have previously been found to show altered expression in schizophrenia brain and to bind to neuregulin, this finding suggests that DKK4 may play a role in schizophrenia pathogenesis.

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