Expanding the range of ZNF804A variants conferring risk of psychosis

S Steinberg, Ole Mors, Anders Børglum, O Gustafsson, T Werge, P B Mortensen, O A Andreassen, E Sigurdsson, T E Thorgeirsson, Y Böttcher, P Olason, R A Ophoff, S Cichon, I H Gudjonsdottir, O P H Pietiläinen, Mette Nyegaard, A Tuulio-Henriksson, A Ingason, Thomas Folkmann Hansen, L AthanasiuJ Suvisaari, J Lonnqvist, T Paunio, A Hartmann, G Jürgens, M Nordentoft, D Hougaard, B Norgaard-Pedersen, R Breuer, H-J Möller, I Giegling, B Glenthøj, H B Rasmussen, M Mattheisen, I Bitter, J M Réthelyi, T Sigmundsson, R Fossdal, U Thorsteinsdottir, M Ruggeri, S Tosato, E Strengman, Genetic Risk and Outcome in Psychosis, L A Kiemeney, I Melle, S Djurovic, L Abramova, V Kaleda, M Walshe, E Bramon, E Vassos

    122 Citations (Scopus)

    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 (P5 × 10 8) associated with schizophrenia earlier. However, one variant, rs1344706T, 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 OR1.08, P0.0029) and, by adding bipolar disorder patients, we also confirmed the association with psychosis (added N609, OR1.09, P0.00065). Furthermore, as it has been proposed that variants such as rs1344706Tcommon and with low relative riskmay 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 (P0.013 for association with psychosis). In addition, we found a ZNF804A CNV in an anxiety patient (P0.0016 for association with the larger set of psychiatric disorders).

    Original languageEnglish
    JournalMolecular Psychiatry
    Volume16
    Issue number1
    Pages (from-to)59-66
    Number of pages8
    ISSN1359-4184
    DOIs
    Publication statusPublished - 1 Jan 2011

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