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, Lambertus A. Kiemeney, Jan Veldink, Leonard van den Berg, Andres Ingason, Pierandrea Muglia, Robin Murray, Markus M. Nöthen, Engilbert Sigurdsson, Hannes Petursson, Unnur Thorsteinsdottir, Augustine Kong, I. Alex Rubino, Marc de Hert, János M. Réthelyi, István Bitter, Erik G. Jönsson, Vera Golimbet, Angel Carracedo, Hannelore Ehrenreich, Nick Craddock, Michael J. Owen, Michael C. O'Donovan, Mirella Ruggeri, Sarah Tosato, Leena Peltonen, Roel A. Ophoff, David A. Collier, David St Clair, Marcella Rietschel, Sven Cichon, Hreinn Stefansson, Dan Rujescu, Kari Stefansson*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

157 Citations (Scopus)


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
Article numberddr325
Pages (from-to)4076-4081
Number of pages6
JournalHuman Molecular Genetics
Issue number20
Publication statusPublished - Oct 2011

Bibliographical note

Funding Information:
This work was supported by the European Union [grant numbers LSHM-CT-2006-037761 (Project SGENE), PIAP-GA-2008-218251 (Project PsychGene), HEALTH-F2-2009-223423 (Project PsychCNVs)]; the National Genome Research Network of the German Federal Ministry of Education and Research (BMBF) [grant numbers 01GS08144 (MooDS-Net), 01GS08147 (NGFNplus)]; the National Institute of Mental Health [R01 MH078075, and N01 MH900001, MH074027 to the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) project]; the Centre of Excellence for Complex Disease Genetics of the Academy of Finland (grant numbers 213506, 129680); the Biocentrum Helsinki Foundation and Research Program for Molecular Medicine, Faculty of Medicine, University of Helsinki; the Stanley Medical Research Institute; the Danish Council for Strategic Research (grant number 2101-07-0059); H. Lundbeck A/S; the Research Council of Norway (grant number 163070/V50); the South-East Norway Health Authority (grant number 2004-123); the Medical Research Council; Ministerio de Sanidad y Consumo, Spain (grant number PI081522 to J.C.); Xunta de Galicia (grant number 08CSA005208PR to A.C.); the Swedish Research Council; the Wellcome Trust (grant number 083948/Z/07/Z as part of the Wellcome Trust Case Control Consortium 2); the Max Planck Society and Eli Lilly and Company (genotyping for CATIE and part of the TOP sample).


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