J Wilkinson

Publications (4)19.43 Total impact

• Article: IGF1, growth pathway polymorphisms and schizophrenia: a pooling study.

  D Gunnell, S Lewis, J Wilkinson, L Georgieva, G Smith Davey, I N M Day, J M P Holly, M C O'Donovan, M J Owen, G Kirov, S Zammit
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  ABSTRACT: It has been hypothesized that insulin-like growth factors (IGFs) and components of the growth-hormone (GH)-IGF axis may underlie reported associations of poor fetal and childhood growth with schizophrenia. We have investigated the association of schizophrenia with 16 SNPs spanning the IGF1 gene with an inter-marker distance of approximately 2-3 kb. We also examined associations with four common functional polymorphisms of genes involved in aspects of the GH-IGF system--the IGF1 receptor (IGF1R), insulin receptor substrate (IRS1), growth hormone (GH1), and IGF binding protein-3 (IGFBP3). The study was based on an analysis of pooled DNA samples from 648 UK and Irish cases of schizophrenia and 712 blood donor controls and of 297 Bulgarian parent offspring trios. In replicated pool analyses, none of the 16 SNPs in IGF1 nor the 4 key SNPs in the other growth pathway genes were associated with schizophrenia. SNP coverage of IGF1 was extensive, so our findings do not support a major role for IGF-I in the aetiology of schizophrenia.
  American Journal of Medical Genetics Part B Neuropsychiatric Genetics 02/2007; 144B(1):117-20. · 3.70 Impact Factor
• Article: IGF1, growth pathway polymorphisms and schizophrenia: A pooling study

  D. Gunnell, S. Lewis, J. Wilkinson, L. Georgieva, G. Smith Davey, I.N.M. Day, J.M.P. Holly, M.C. O'Donovan, M.J. Owen, G. Kirov, S. Zammit
  [show abstract] [hide abstract]
  ABSTRACT: It has been hypothesized that insulin-like growth factors (IGFs) and components of the growth-hormone (GH)-IGF axis may underlie reported associations of poor fetal and childhood growth with schizophrenia. We have investigated the association of schizophrenia with 16 SNPs spanning the IGF1 gene with an inter-marker distance of approximately 2–3 kb. We also examined associations with four common functional polymorphisms of genes involved in aspects of the GH-IGF system—the IGF1 receptor (IGF1R), insulin receptor substrate (IRS1), growth hormone (GH1), and IGF binding protein-3 (IGFBP3). The study was based on an analysis of pooled DNA samples from 648 UK and Irish cases of schizophrenia and 712 blood donor controls and of 297 Bulgarian parent offspring trios. In replicated pool analyses, none of the 16 SNPs in IGF1 nor the 4 key SNPs in the other growth pathway genes were associated with schizophrenia. SNP coverage of IGF1 was extensive, so our findings do not support a major role for IGF-I in the aetiology of schizophrenia. © 2006 Wiley-Liss, Inc.
  American Journal of Medical Genetics Part B Neuropsychiatric Genetics 01/2007; 144B(1):117 - 120. · 3.70 Impact Factor
• Article: Convergent evidence that oligodendrocyte lineage transcription factor 2 (OLIG2) and interacting genes influence susceptibility to schizophrenia

  L. Georgieva, V. Moskvina, T. Peirce, N. Norton, N.J. Bray, L. Jones, P. Holmans, S. Macgregor, S. Zammit, J. Wilkinson, [......], I. Nikolov, N. Williams, D. Ivanov, K.L. Davis, V. Haroutunian, J.D. Buxbaum, N. Craddock, G. Kirov, M.J. Owen, M.C. O'Donovan
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  ABSTRACT: Abnormal oligodendrocyte function has been postulated as a primary etiological event in schizophrenia. Oligodendrocyte lineage transcription factor 2 (OLIG2) encodes a transcription factor central to oligodendrocyte development. Analysis of OLIG2 in a case-control sample (n = approximately 1,400) in the U.K. revealed several SNPs to be associated with schizophrenia (minimum P = 0.0001, gene-wide P = 0.0009). To obtain independent support for this association, we sought evidence for genetic interaction between OLIG2 and three genes of relevance to oligodendrocyte function for which we have reported evidence for association with schizophrenia: CNP, NRG1, and ERBB4. We found interaction effects on disease risk between OLIG2 and CNP (minimum P = 0.0001, corrected P = 0.008) for interaction with ERBB4 (minimum P = 0.002, corrected P = 0.04) but no evidence for interaction with NRG1. To investigate the biological plausibility of the interactions, we sought correlations between the expression of the genes. The results were similar to those of the genetic interaction analysis. OLIG2 expression significantly correlated in cerebral cortex with CNP (P < 10(-7)) and ERBB4 (P = 0.002, corrected P = 0.038) but not NRG1. In mouse striatum, Olig2 and Cnp expression also was correlated, and linkage analysis for trans-effects on gene expression suggests that each locus regulates the other's expression. Our data provide strong convergent evidence that variation in OLIG2 confers susceptibility to schizophrenia alone and as part of a network of genes implicated in oligodendrocyte function
  Proc.Natl.Acad.Sci.U.S.A. 08/2006; 103(33).
• Article: Identification in 2 independent samples of a novel schizophrenia risk haplotype of the dystrobrevin binding protein gene (DTNBP1).

  N M Williams, A Preece, D W Morris, G Spurlock, N J Bray, M Stephens, N Norton, H Williams, M Clement, S Dwyer, C Curran, J Wilkinson, V Moskvina, J L Waddington, M Gill, A P Corvin, S Zammit, G Kirov, M J Owen, M C O'Donovan
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  ABSTRACT: Recent research suggests that variation in the gene encoding dystrobrevin binding protein (DTNBP1) confers susceptibility to schizophrenia. Thus far, no specific risk haplotype has been identified in more than 1 study. To confirm DTNBP1 as a schizophrenia susceptibility gene, to identify and replicate specific risk and protective haplotypes, and to explore relationships between DTNBP1 and the phenotype. Genetic association study based on mutation detection and case-control analysis. All subjects were unrelated and ascertained from general (secondary care) psychiatric inpatient and outpatient services. The Cardiff, Wales, sample included 708 white subjects from the United Kingdom and Ireland (221 females) who met DSM-IV criteria for schizophrenia and were individually matched for age, sex, and ethnicity to 711 blood donor controls (233 females). Mean +/- SD age at first psychiatric contact for cases was 23.6 +/- 7.7 years; mean age at ascertainment was 41.8 +/- 13.5 years. The Dublin, Ireland, sample included 219 white subjects from the Republic of Ireland who met DSM-III-R criteria for schizophrenia or schizoaffective disorder and 231 controls. The mean age of the Irish cases was 46.0 +/- 8.5 years; mean age at first psychiatric contact was 25.2 +/- 12.4 years. Evidence for association between the DTNBP1 locus and schizophrenia. In the Cardiff sample, there was no evidence for association with previously implicated haplotypes but strong evidence for association with multiple novel haplotypes. Maximum evidence was found for a novel 3-marker haplotype (global P<.001), composed of 1 risk haplotype (P =.01) and 2 protective haplotypes, 1 common (P =.006) and 1 rare (P<.001). Specific risk and protective haplotypes were replicated in the Dublin sample (P =.02,.047, and.006, respectively). The only phenotypic variable associated with any haplotype was between the common protective haplotype and higher educational achievement (P =.02, corrected for multiple tests). DTNBP1 is a susceptibility gene for schizophrenia. Specific risk and protective haplotypes were identified and replicated. Association with educational achievement may suggest protection mediated by IQ, although this needs to be confirmed in an independent data set.
  Archives of General Psychiatry 04/2004; 61(4):336-44. · 12.02 Impact Factor