Journal Article PreJuSER-14635

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Expanding the range of ZNF804A variants conferring risk of psychosis

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2011
Macmillan London

Molecular psychiatry 16, 59 - 66 () [10.1038/mp.2009.149]

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Abstract: A trio of genome-wide association studies recently reported sequence variants at three loci to be significantly associated with schizophrenia. No sequence polymorphism had been unequivocally (P<5 × 10(-8)) associated with schizophrenia earlier. However, one variant, rs1344706[T], had come very close. This polymorphism, located in an intron of ZNF804A, was reported to associate with schizophrenia with a P-value of 1.6 × 10(-7), and with psychosis (schizophrenia plus bipolar disorder) with a P-value of 1.0 × 10(-8). In this study, using 5164 schizophrenia cases and 20,709 controls, we replicated the association with schizophrenia (odds ratio OR = 1.08, P = 0.0029) and, by adding bipolar disorder patients, we also confirmed the association with psychosis (added N = 609, OR = 1.09, P = 0.00065). Furthermore, as it has been proposed that variants such as rs1344706[T]-common and with low relative risk-may also serve to identify regions harboring less common, higher-risk susceptibility alleles, we searched ZNF804A for large copy number variants (CNVs) in 4235 psychosis patients, 1173 patients with other psychiatric disorders and 39,481 controls. We identified two CNVs including at least part of ZNF804A in psychosis patients and no ZNF804A CNVs in controls (P = 0.013 for association with psychosis). In addition, we found a ZNF804A CNV in an anxiety patient (P = 0.0016 for association with the larger set of psychiatric disorders).

Keyword(s): Anxiety Disorders: genetics (MeSH) ; Bipolar Disorder: genetics (MeSH) ; Case-Control Studies (MeSH) ; DNA Copy Number Variations: genetics (MeSH) ; Genetic Predisposition to Disease (MeSH) ; Genome-Wide Association Study (MeSH) ; Humans (MeSH) ; Kruppel-Like Transcription Factors: genetics (MeSH) ; Reference Values (MeSH) ; Schizophrenia: genetics (MeSH) ; Kruppel-Like Transcription Factors ; ZNF804A protein, human ; J ; schizophrenia (auto) ; bipolar disorder (auto) ; ZNF804A (auto) ; CNV (auto) ; association (auto)


Note: We thank the subjects, their families and the recruitment center staff. This work was supported by the European Union (LSHM-CT-2006-037761 (Project SGENE), PIAP-GA-2008-218251 (Project PsychGene) and HEALTH-F2-2009-223423 (Project PsychCNVs)), the National Genomic Network (NGFN-2) of the German Federal Ministry of Education and Research (BMBF), the National Institute of Mental Health (R01 MH078075), the Center of Excellence for Complex Disease Genetics of the Academy of Finland (Grants 213506, 129680) and the Biocentrum Helsinki Foundation and Research Program for Molecular Medicine, Faculty of Medicine, University of Helsinki.

Contributing Institute(s):
  1. Strukturelle und funktionelle Organisation des Gehirns (INM-1)
Research Program(s):
  1. Funktion und Dysfunktion des Nervensystems (FUEK409) (FUEK409)
  2. 89571 - Connectivity and Activity (POF2-89571) (POF2-89571)
  3. PSYCHGENE - Copy Number Variation and Endophenotypes in Psychiatric Disorders (218251) (218251)
  4. PSYCHCNVS - Copy number variations conferring risk of psychiatric disorders in children (223423) (223423)

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 Record created 2012-11-13, last modified 2021-01-29


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