Fine mapping of ZNF 804 A and genome-wide significant evidence for its involvement in schizophrenia and bipolar disorder

A recent genome wide association study 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). Here we provide additional evidence for association through meta-analysis of a larger dataset (schizophrenia/schizoaffective disorder N = 18945, schizophrenia plus bipolar disorder N =21274, *corresponding authors; Michael C O’Donovan and Michael J Owen, MRC Centre for Neuropsychiatric Genetics and Genomics, Henry Wellcome Building, Department of Psychological Medicine and Neurology, School of Medicine, Cardiff University, Cardiff, CF14 4XN, UK. Telephone: 44 (0)2920687066 Fax: 44 (0)2920687068 odonovanmc@Cardiff.ac.uk/owenmj@Cardiff.ac.uk. The authors declare no conflicts of interest. NIH Public Access Author Manuscript Mol Psychiatry. Author manuscript; available in PMC 2014 February 10. Published in final edited form as: Mol Psychiatry. 2011 April ; 16(4): 429–441. doi:10.1038/mp.2010.36. N IH PA Athor M anscript N IH PA Athor M anscript N IH PA Athor M anscript controls N =38675). 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 LD mapping. 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, OR=1.10, 95% CI 1.07–1.14) and schizophrenia and bipolar disorder combined (P=4.1 ×10−13, OR=1.11, 95% CI 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.

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