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Association analysis of the chromosome 4p15-p16 candidate region for bipolar disorder and schizophrenia.
Christoforou, A; Le Hellard, S; Thomson, P A; Morris, S W; Tenesa, A; Pickard, B S; Wray, N R; Muir, W J; Blackwood, D H; Porteous, D J; Evans, K L.
Afiliación
  • Christoforou A; Medical Genetics Section, Molecular Medicine Centre, Western General Hospital, University of Edinburgh, Edinburgh, UK. a.christoforou@ed.ac.uk
Mol Psychiatry ; 12(11): 1011-25, 2007 Nov.
Article en En | MEDLINE | ID: mdl-17457313
ABSTRACT
Several independent linkage studies have identified chromosome 4p15-p16 as a putative region of susceptibility for bipolar disorder (BP), schizophrenia (SCZ) and related phenotypes. Previously, we identified two subregions (B and D) of the 4p15-p16 region that are shared by three of four 4p-linked families examined. Here, we describe a large-scale association analysis of regions B and D (3.8 and 4.5 Mb, respectively). We selected 408 haplotype-tagging single nucleotide polymorphisms (SNPs) on a block-by-block basis from the International HapMap project and tested them in 368 BP, 386 SCZ and 458 control individuals. Nominal significance thresholds were determined using principal component analysis as implemented in the program SNPSpD. In region B, overlapping SNPs and haplotypes met the region-wide threshold (Phaplotype test level and clustered in two regions. In region D, no individual SNPs were nominally significant, but multiple global and individual haplotypes were associated with BP and/or SCZ (region-wide threshold, Phaplotypes fell into two regions. Within each of these four clusters, at least one globally significant haplotype withstood permutation testing (P(gp)genes were found within these associated regions, while Known/RefSeq genes, including KIAA0746 and PPARGC1A, mapped nearby. There were also nine other clusters within regions B and D with nominally significant haplotypes, but only at the individual haplotype level. KIAA0746, PPARGC1A, GPR125, CCKAR and DKFZp761B107 overlapped with these regions. This study has identified significant associations between BP and SCZ within the chromosome 4p linkage region, resulting in candidate regions worthy of further investigation.
Asunto(s)
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Base de datos: MEDLINE Asunto principal: Esquizofrenia / Trastorno Bipolar / Cromosomas Humanos Par 4 / Predisposición Genética a la Enfermedad / Polimorfismo de Nucleótido Simple Tipo de estudio: Prognostic_studies / Risk_factors_studies Límite: Female / Humans / Male Idioma: En Revista: Mol Psychiatry Asunto de la revista: BIOLOGIA MOLECULAR / PSIQUIATRIA Año: 2007 Tipo del documento: Article País de afiliación: Reino Unido
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Base de datos: MEDLINE Asunto principal: Esquizofrenia / Trastorno Bipolar / Cromosomas Humanos Par 4 / Predisposición Genética a la Enfermedad / Polimorfismo de Nucleótido Simple Tipo de estudio: Prognostic_studies / Risk_factors_studies Límite: Female / Humans / Male Idioma: En Revista: Mol Psychiatry Asunto de la revista: BIOLOGIA MOLECULAR / PSIQUIATRIA Año: 2007 Tipo del documento: Article País de afiliación: Reino Unido