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

Williams, Hywel John ORCID:, Norton, Nadine ORCID:, Dwyer, Sarah Lynne, Escott-Price, Valentina ORCID:, Nikolov, Ivan, Carroll, Liam, Georgieva, Lyudmila, Williams, Nigel Melville ORCID:, Morris, D. W., Quinn, E. M., Giegling, I., Ikeda, Masashi, Wood, J., Lencz, T., Hultman, C., Lichtenstein, P., Thiselton, D., Maher, B. S., Molecular Genetics of Schizophrenia Collaboration (MGS), International Schizophrenia Consortium (ISC), SGENE-plus, GROUP, Malhotra, A. K., Riley, B., Kendler, K. S., Gill, M., Sullivan, P., Sklar, P., Purcell, S., Nimgaonkar, V. L., Kirov, George ORCID:, Corvin, A., Holmans, Peter ALan ORCID:, Rujescu, D., Craddock, Nicholas John ORCID:, Owen, Michael John ORCID: and O'Donovan, Michael Conlon ORCID: 2011. Fine mapping of ZNF804A and genome-wide significant evidence for its involvement in schizophrenia and bipolar disorder. Molecular Psychiatry 16 (4) , pp. 429-441. 10.1038/mp.2010.36

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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
Date Type: Publication
Status: Published
Schools: Neuroscience and Mental Health Research Institute (NMHRI)
MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Systems Immunity Research Institute (SIURI)
Subjects: R Medicine > RZ Other systems of medicine
Uncontrolled Keywords: ZNF804A; association; schizophrenia; bipolar disorder; meta-analysis
Publisher: Nature Publishing Group
ISSN: 1359-4184
Last Modified: 06 Nov 2022 13:48

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