Fine mapping of ZNF804A and genome-wide significant evidence for its involvement in schizophrenia and bipolar disorder.

Hdl Handle:
http://hdl.handle.net/10147/238807
Title:
Fine mapping of ZNF804A and genome-wide significant evidence for its involvement in schizophrenia and bipolar disorder.
Authors:
Williams, H J; Norton, N; Dwyer, S; Moskvina, V; Nikolov, I; Carroll, L; Georgieva, L; Williams, N M; Morris, D W; Quinn, E M; Giegling, I; Ikeda, M; Wood, J; Lencz, T; Hultman, C; Lichtenstein, P; Thiselton, D; Maher, B S; Malhotra, A K; Riley, B; Kendler, K S; Gill, M; Sullivan, P; Sklar, P; Purcell, S; Nimgaonkar, V L; Kirov, G; Holmans, P; Corvin, A; Rujescu, D; Craddock, N; Owen, M J; O'Donovan, M C
Affiliation:
MRC Centre for Neuropsychiatric Genetics and Genomics, Department of Psychological Medicine and Neurology, School of Medicine, Cardiff University, Cardiff, UK.
Citation:
Fine mapping of ZNF804A and genome-wide significant evidence for its involvement in schizophrenia and bipolar disorder. 2011, 16 (4):429-41 Mol. Psychiatry
Journal:
Molecular psychiatry
Issue Date:
Apr-2011
URI:
http://hdl.handle.net/10147/238807
DOI:
10.1038/mp.2010.36
PubMed ID:
20368704
Abstract:
A recent genome-wide association study (GWAS) reported evidence for association between rs1344706 within ZNF804A (encoding zinc-finger protein 804A) and schizophrenia (P=1.61 × 10(-7)), and stronger evidence when the phenotype was broadened to include bipolar disorder (P=9.96 × 10(-9)). In this study we provide additional evidence for association through meta-analysis of a larger data set (schizophrenia/schizoaffective disorder N=18 945, schizophrenia plus bipolar disorder N=21 274 and controls N=38 675). We also sought to better localize the association signal using a combination of de novo polymorphism discovery in exons, pooled de novo polymorphism discovery spanning the genomic sequence of the locus and high-density linkage disequilibrium (LD) mapping. The meta-analysis provided evidence for association between rs1344706 that surpasses widely accepted benchmarks of significance by several orders of magnitude for both schizophrenia (P=2.5 × 10(-11), odds ratio (OR) 1.10, 95% confidence interval 1.07-1.14) and schizophrenia and bipolar disorder combined (P=4.1 × 10(-13), OR 1.11, 95% confidence interval 1.07-1.14). After de novo polymorphism discovery and detailed association analysis, rs1344706 remained the most strongly associated marker in the gene. The allelic association at the ZNF804A locus is now one of the most compelling in schizophrenia to date, and supports the accumulating data suggesting overlapping genetic risk between schizophrenia and bipolar disorder.
Item Type:
Article
Language:
en
MeSH:
Adult; Aged; Bipolar Disorder; Chromosome Mapping; Europe; Exons; Female; Gene Frequency; Genetic Predisposition to Disease; Genome-Wide Association Study; Genotype; Humans; Kruppel-Like Transcription Factors; Linkage Disequilibrium; Male; Meta-Analysis as Topic; Middle Aged; Odds Ratio; Polymorphism, Single Nucleotide; Quantitative Trait Loci; Schizophrenia
ISSN:
1476-5578

Full metadata record

DC FieldValue Language
dc.contributor.authorWilliams, H Jen_GB
dc.contributor.authorNorton, Nen_GB
dc.contributor.authorDwyer, Sen_GB
dc.contributor.authorMoskvina, Ven_GB
dc.contributor.authorNikolov, Ien_GB
dc.contributor.authorCarroll, Len_GB
dc.contributor.authorGeorgieva, Len_GB
dc.contributor.authorWilliams, N Men_GB
dc.contributor.authorMorris, D Wen_GB
dc.contributor.authorQuinn, E Men_GB
dc.contributor.authorGiegling, Ien_GB
dc.contributor.authorIkeda, Men_GB
dc.contributor.authorWood, Jen_GB
dc.contributor.authorLencz, Ten_GB
dc.contributor.authorHultman, Cen_GB
dc.contributor.authorLichtenstein, Pen_GB
dc.contributor.authorThiselton, Den_GB
dc.contributor.authorMaher, B Sen_GB
dc.contributor.authorMalhotra, A Ken_GB
dc.contributor.authorRiley, Ben_GB
dc.contributor.authorKendler, K Sen_GB
dc.contributor.authorGill, Men_GB
dc.contributor.authorSullivan, Pen_GB
dc.contributor.authorSklar, Pen_GB
dc.contributor.authorPurcell, Sen_GB
dc.contributor.authorNimgaonkar, V Len_GB
dc.contributor.authorKirov, Gen_GB
dc.contributor.authorHolmans, Pen_GB
dc.contributor.authorCorvin, Aen_GB
dc.contributor.authorRujescu, Den_GB
dc.contributor.authorCraddock, Nen_GB
dc.contributor.authorOwen, M Jen_GB
dc.contributor.authorO'Donovan, M Cen_GB
dc.date.accessioned2012-08-15T14:25:48Z-
dc.date.available2012-08-15T14:25:48Z-
dc.date.issued2011-04-
dc.identifier.citationFine mapping of ZNF804A and genome-wide significant evidence for its involvement in schizophrenia and bipolar disorder. 2011, 16 (4):429-41 Mol. Psychiatryen_GB
dc.identifier.issn1476-5578-
dc.identifier.pmid20368704-
dc.identifier.doi10.1038/mp.2010.36-
dc.identifier.urihttp://hdl.handle.net/10147/238807-
dc.description.abstractA recent genome-wide association study (GWAS) reported evidence for association between rs1344706 within ZNF804A (encoding zinc-finger protein 804A) and schizophrenia (P=1.61 × 10(-7)), and stronger evidence when the phenotype was broadened to include bipolar disorder (P=9.96 × 10(-9)). In this study we provide additional evidence for association through meta-analysis of a larger data set (schizophrenia/schizoaffective disorder N=18 945, schizophrenia plus bipolar disorder N=21 274 and controls N=38 675). We also sought to better localize the association signal using a combination of de novo polymorphism discovery in exons, pooled de novo polymorphism discovery spanning the genomic sequence of the locus and high-density linkage disequilibrium (LD) mapping. The meta-analysis provided evidence for association between rs1344706 that surpasses widely accepted benchmarks of significance by several orders of magnitude for both schizophrenia (P=2.5 × 10(-11), odds ratio (OR) 1.10, 95% confidence interval 1.07-1.14) and schizophrenia and bipolar disorder combined (P=4.1 × 10(-13), OR 1.11, 95% confidence interval 1.07-1.14). After de novo polymorphism discovery and detailed association analysis, rs1344706 remained the most strongly associated marker in the gene. The allelic association at the ZNF804A locus is now one of the most compelling in schizophrenia to date, and supports the accumulating data suggesting overlapping genetic risk between schizophrenia and bipolar disorder.en_GB
dc.language.isoenen
dc.rightsArchived with thanks to Molecular psychiatryen_GB
dc.subject.meshAdult-
dc.subject.meshAged-
dc.subject.meshBipolar Disorder-
dc.subject.meshChromosome Mapping-
dc.subject.meshEurope-
dc.subject.meshExons-
dc.subject.meshFemale-
dc.subject.meshGene Frequency-
dc.subject.meshGenetic Predisposition to Disease-
dc.subject.meshGenome-Wide Association Study-
dc.subject.meshGenotype-
dc.subject.meshHumans-
dc.subject.meshKruppel-Like Transcription Factors-
dc.subject.meshLinkage Disequilibrium-
dc.subject.meshMale-
dc.subject.meshMeta-Analysis as Topic-
dc.subject.meshMiddle Aged-
dc.subject.meshOdds Ratio-
dc.subject.meshPolymorphism, Single Nucleotide-
dc.subject.meshQuantitative Trait Loci-
dc.subject.meshSchizophrenia-
dc.titleFine mapping of ZNF804A and genome-wide significant evidence for its involvement in schizophrenia and bipolar disorder.en_GB
dc.typeArticleen
dc.contributor.departmentMRC Centre for Neuropsychiatric Genetics and Genomics, Department of Psychological Medicine and Neurology, School of Medicine, Cardiff University, Cardiff, UK.en_GB
dc.identifier.journalMolecular psychiatryen_GB
dc.description.provinceLeinsteren

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