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; 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

doi:10.1093/hmg/ddr325

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

Applied Medicine

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168 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 language	English
Pages (from-to)	4076-4081
Number of pages	6
Journal	Human Molecular Genetics
Volume	20
Issue number	20
Early online date	26 Jul 2011
DOIs	https://doi.org/10.1093/hmg/ddr325
Publication status	Published - 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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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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

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

@article{9d87dc9894f54bbfb8bcbff8013b03cb,

title = "Common variants at VRK2 and TCF4 conferring risk of schizophrenia",

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)).",

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",

author = "Stacy Steinberg and {de Jong}, Simone and Andreassen, {Ole A} and Thomas Werge and B{\o}rglum, {Anders D} and Ole Mors and Mortensen, {Preben B} and Omar Gustafsson and Javier Costas and Pietil{\"a}inen, {Olli P H} and Ditte Demontis and Sergi Papiol and Johanna Huttenlocher and Manuel Mattheisen and Ren{\'e} Breuer and Evangelos Vassos and Ina Giegling and Gillian Fraser and Nicholas Walker and Annamari Tuulio-Henriksson and Jaana Suvisaari and Jouko L{\"o}nnqvist and Tiina Paunio and Ingrid Agartz and Ingrid Melle and Srdjan Djurovic and Eric Strengman and Gesche J{\"u}rgens and Birte Glenth{\o}j and Lars Terenius and Hougaard, {David M} and Torben {\O}rntoft and Carsten Wiuf and Michael Didriksen and Hollegaard, {Mads V} and Merete Nordentoft and {van Winkel}, Ruud and Gunter Kenis and Lilia Abramova and Vasily Kaleda and Manuel Arrojo and Julio Sanju{\'a}n and Celso Arango and Swetlana Sperling and Moritz Rossner and Michele Ribolsi and Valentina Magni and Alberto Siracusano and Claus Christiansen and {St Clair}, David and {Irish Schizophrenia Genomics Consortium}",

year = "2011",

month = oct,

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doi = "10.1093/hmg/ddr325",

language = "English",

volume = "20",

pages = "4076--4081",

journal = "Human Molecular Genetics",

publisher = "Oxford University Press",

number = "20",

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TY - JOUR

T1 - Common variants at VRK2 and TCF4 conferring risk of schizophrenia

AU - Steinberg, Stacy

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

PY - 2011/10/15

Y1 - 2011/10/15

N2 - 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)).

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)).

KW - alleles

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

U2 - 10.1093/hmg/ddr325

DO - 10.1093/hmg/ddr325

M3 - Article

C2 - 21791550

VL - 20

SP - 4076

EP - 4081

JO - Human Molecular Genetics

JF - Human Molecular Genetics

IS - 20

ER -

Common variants at VRK2 and TCF4 conferring risk of schizophrenia

Abstract

Keywords

UN SDGs

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