Common variants at VRK2 and TCF4 conferring risk of schizophrenia

Stacy Steinberg, Simone de Jong, Ole A Andreassen, Thomas Werge, Anders D Børglum, Ole Mors, Preben B Mortensen, Omar Gustafsson, Javier Costas, Olli P H Pietiläinen, Ditte Demontis, Sergi Papiol, Johanna Huttenlocher, Manuel Mattheisen, René Breuer, Evangelos Vassos, Ina Giegling, Gillian Fraser, Nicholas Walker, Annamari Tuulio-HenrikssonJaana Suvisaari, Jouko Lönnqvist, Tiina Paunio, Ingrid Agartz, Ingrid Melle, Srdjan Djurovic, Eric Strengman, Gesche Jürgens, Birte Glenthøj, Lars Terenius, David M Hougaard, Torben Ørntoft, Carsten Wiuf, Michael Didriksen, Mads V Hollegaard, Merete Nordentoft, Ruud van Winkel, Gunter Kenis, Lilia Abramova, Vasily Kaleda, Manuel Arrojo, Julio Sanjuán, Celso Arango, Swetlana Sperling, Moritz Rossner, Michele Ribolsi, Valentina Magni, Alberto Siracusano, Claus Christiansen, David St Clair, Irish Schizophrenia Genomics Consortium

Research output: Contribution to journalArticle

147 Citations (Scopus)

Abstract

Common sequence variants have recently joined rare structural polymorphisms as genetic factors with strong evidence for association with schizophrenia. Here we extend our previous genome-wide association study and meta-analysis (totalling 7 946 cases and 19 036 controls) by examining an expanded set of variants using an enlarged follow-up sample (up to 10 260 cases and 23 500 controls). In addition to previously reported alleles in the major histocompatibility complex region, near neurogranin (NRGN) and in an intron of transcription factor 4 (TCF4), we find two novel variants showing genome-wide significant association: rs2312147[C], upstream of vaccinia-related kinase 2 (VRK2) [odds ratio (OR) = 1.09, P = 1.9 × 10(-9)] and rs4309482[A], between coiled-coiled domain containing 68 (CCDC68) and TCF4, about 400 kb from the previously described risk allele, but not accounted for by its association (OR = 1.09, P = 7.8 × 10(-9)).
Original languageEnglish
Pages (from-to)4076-4081
Number of pages6
JournalHuman Molecular Genetics
Volume20
Issue number20
Early online date26 Jul 2011
DOIs
Publication statusPublished - 15 Oct 2011

Keywords

  • alleles
  • basic helix-loop-helix leucine zipper transcription factors
  • genetic predisposition to disease
  • genome-wide association study
  • genotype
  • humans
  • polymorphism, single nucleotide
  • protein-serine-threonine kinases
  • risk
  • schizophrenia
  • transcription factors

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    Steinberg, S., de Jong, S., Andreassen, O. A., Werge, T., Børglum, A. D., Mors, O., Mortensen, P. B., Gustafsson, O., Costas, J., Pietiläinen, O. P. H., Demontis, D., Papiol, S., Huttenlocher, J., Mattheisen, M., Breuer, R., Vassos, E., Giegling, I., Fraser, G., Walker, N., ... Irish Schizophrenia Genomics Consortium (2011). Common variants at VRK2 and TCF4 conferring risk of schizophrenia. Human Molecular Genetics, 20(20), 4076-4081. https://doi.org/10.1093/hmg/ddr325