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-Henriksson & 31 others Jaana 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

140 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

Fingerprint

Vaccinia
Neurogranin
Schizophrenia
Transcription Factors
Phosphotransferases
Alleles
Odds Ratio
Genome-Wide Association Study
Major Histocompatibility Complex
Introns
Meta-Analysis
Genome

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

Cite this

Steinberg, S., de Jong, S., Andreassen, O. A., Werge, T., Børglum, A. D., Mors, O., ... 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

Common variants at VRK2 and TCF4 conferring risk of schizophrenia. / Steinberg, Stacy; de Jong, Simone; Andreassen, Ole A; Werge, Thomas; Børglum, Anders D; Mors, Ole; Mortensen, Preben B; Gustafsson, Omar; Costas, Javier; Pietiläinen, Olli P H; Demontis, Ditte; Papiol, Sergi; Huttenlocher, Johanna; Mattheisen, Manuel; Breuer, René; Vassos, Evangelos; Giegling, Ina; Fraser, Gillian; Walker, Nicholas; Tuulio-Henriksson, Annamari; Suvisaari, Jaana; Lönnqvist, Jouko; Paunio, Tiina; Agartz, Ingrid; Melle, Ingrid; Djurovic, Srdjan; Strengman, Eric; Jürgens, Gesche; Glenthøj, Birte; Terenius, Lars; Hougaard, David M; Ørntoft, Torben; Wiuf, Carsten; Didriksen, Michael; Hollegaard, Mads V; Nordentoft, Merete; van Winkel, Ruud; Kenis, Gunter; Abramova, Lilia; Kaleda, Vasily; Arrojo, Manuel; Sanjuán, Julio; Arango, Celso; Sperling, Swetlana; Rossner, Moritz; Ribolsi, Michele; Magni, Valentina; Siracusano, Alberto; Christiansen, Claus; St Clair, David; Irish Schizophrenia Genomics Consortium.

In: Human Molecular Genetics, Vol. 20, No. 20, 15.10.2011, p. 4076-4081.

Research output: Contribution to journalArticle

Steinberg, S, de Jong, S, Andreassen, OA, Werge, T, Børglum, AD, Mors, O, Mortensen, PB, Gustafsson, O, Costas, J, Pietiläinen, OPH, Demontis, D, Papiol, S, Huttenlocher, J, Mattheisen, M, Breuer, R, Vassos, E, Giegling, I, Fraser, G, Walker, N, Tuulio-Henriksson, A, Suvisaari, J, Lönnqvist, J, Paunio, T, Agartz, I, Melle, I, Djurovic, S, Strengman, E, Jürgens, G, Glenthøj, B, Terenius, L, Hougaard, DM, Ørntoft, T, Wiuf, C, Didriksen, M, Hollegaard, MV, Nordentoft, M, van Winkel, R, Kenis, G, Abramova, L, Kaleda, V, Arrojo, M, Sanjuán, J, Arango, C, Sperling, S, Rossner, M, Ribolsi, M, Magni, V, Siracusano, A, Christiansen, C, St Clair, D & Irish Schizophrenia Genomics Consortium 2011, 'Common variants at VRK2 and TCF4 conferring risk of schizophrenia', Human Molecular Genetics, vol. 20, no. 20, pp. 4076-4081. https://doi.org/10.1093/hmg/ddr325
Steinberg S, de Jong S, Andreassen OA, Werge T, Børglum AD, Mors O et al. Common variants at VRK2 and TCF4 conferring risk of schizophrenia. Human Molecular Genetics. 2011 Oct 15;20(20):4076-4081. https://doi.org/10.1093/hmg/ddr325
Steinberg, Stacy ; de Jong, Simone ; Andreassen, Ole A ; Werge, Thomas ; Børglum, Anders D ; Mors, Ole ; Mortensen, Preben B ; Gustafsson, Omar ; Costas, Javier ; Pietiläinen, Olli P H ; Demontis, Ditte ; Papiol, Sergi ; Huttenlocher, Johanna ; Mattheisen, Manuel ; Breuer, René ; Vassos, Evangelos ; Giegling, Ina ; Fraser, Gillian ; Walker, Nicholas ; Tuulio-Henriksson, Annamari ; Suvisaari, Jaana ; Lönnqvist, Jouko ; Paunio, Tiina ; Agartz, Ingrid ; Melle, Ingrid ; Djurovic, Srdjan ; Strengman, Eric ; Jürgens, Gesche ; Glenthøj, Birte ; Terenius, Lars ; Hougaard, David M ; Ørntoft, Torben ; Wiuf, Carsten ; Didriksen, Michael ; Hollegaard, Mads V ; Nordentoft, Merete ; van Winkel, Ruud ; Kenis, Gunter ; Abramova, Lilia ; Kaleda, Vasily ; Arrojo, Manuel ; Sanjuán, Julio ; Arango, Celso ; Sperling, Swetlana ; Rossner, Moritz ; Ribolsi, Michele ; Magni, Valentina ; Siracusano, Alberto ; Christiansen, Claus ; St Clair, David ; Irish Schizophrenia Genomics Consortium. / Common variants at VRK2 and TCF4 conferring risk of schizophrenia. In: Human Molecular Genetics. 2011 ; Vol. 20, No. 20. pp. 4076-4081.
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AU - de Jong, Simone

AU - Andreassen, Ole A

AU - Werge, Thomas

AU - Børglum, Anders D

AU - Mors, Ole

AU - Mortensen, Preben B

AU - Gustafsson, Omar

AU - Costas, Javier

AU - Pietiläinen, Olli P H

AU - Demontis, Ditte

AU - Papiol, Sergi

AU - Huttenlocher, Johanna

AU - Mattheisen, Manuel

AU - Breuer, René

AU - Vassos, Evangelos

AU - Giegling, Ina

AU - Fraser, Gillian

AU - Walker, Nicholas

AU - Tuulio-Henriksson, Annamari

AU - Suvisaari, Jaana

AU - Lönnqvist, Jouko

AU - Paunio, Tiina

AU - Agartz, Ingrid

AU - Melle, Ingrid

AU - Djurovic, Srdjan

AU - Strengman, Eric

AU - Jürgens, Gesche

AU - Glenthøj, Birte

AU - Terenius, Lars

AU - Hougaard, David M

AU - Ørntoft, Torben

AU - Wiuf, Carsten

AU - Didriksen, Michael

AU - Hollegaard, Mads V

AU - Nordentoft, Merete

AU - van Winkel, Ruud

AU - Kenis, Gunter

AU - Abramova, Lilia

AU - Kaleda, Vasily

AU - Arrojo, Manuel

AU - Sanjuán, Julio

AU - Arango, Celso

AU - Sperling, Swetlana

AU - Rossner, Moritz

AU - Ribolsi, Michele

AU - Magni, Valentina

AU - Siracusano, Alberto

AU - Christiansen, Claus

AU - St Clair, David

AU - Irish Schizophrenia Genomics Consortium

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AB - 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)).

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KW - basic helix-loop-helix leucine zipper transcription factors

KW - genetic predisposition to disease

KW - genome-wide association study

KW - genotype

KW - humans

KW - polymorphism, single nucleotide

KW - protein-serine-threonine kinases

KW - risk

KW - schizophrenia

KW - transcription factors

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DO - 10.1093/hmg/ddr325

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JO - Human Molecular Genetics

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