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)).

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Affiliated Institutions

• Copenhagen University Hospital DK
• Hospital General Universitario Gregorio Marañón ES
• King's College London GB
• Universitat de València ES
• European Graduate School of Neuroscience NL
• University of Bonn DE
• Life & Brain (Germany) DE
• University of Oslo
• Broad Institute US
• Nanoscale Microscopy and Molecular Physiology of the Brain Cluster of Excellence 171 — DFG Research Center 103 DE
• University of Aberdeen GB
• Ludwig-Maximilians-Universität München DE
• Karolinska Institutet SE
• deCODE Genetics (Iceland) IS
• University of Rome Tor Vergata IT
• Glostrup Hospital DK
• Institute for Molecular Medicine Finland FI
• Lundbeck (Denmark) DK
• Royal Cornhill Hospital GB
• Finnish Institute for Health and Welfare FI
• University of Helsinki FI
• Bispebjerg Hospital DK
• Complexo Hospitalario Universitario A Coruña ES
• University Medical Center Utrecht NL
• Semmelweis University HU
• Cardiff University GB
• Hologic (Germany) DE
• Centre for Biomedical Network Research on Rare Diseases ES
• KU Leuven BE
• University of Tübingen DE
• Central Institute of Mental Health DE
• GlaxoSmithKline (Italy) IT
• Servicio Gallego de Salud ES
• Aarhus University DK
• Aarhus University Hospital DK
• Nordic Bioscience (Denmark) DK
• Max Planck Institute of Experimental Medicine DE
• Maastricht University Medical Centre NL
• University of Verona IT
• Centro de Investigación Biomédica en Red de Salud Mental ES
• Fundación Pública Galega de Medicina Xenómica ES
• University of Iceland IS
• Oslo University Hospital
• Statens Serum Institut DK
• Mental Health Research Center of Russian Academy of Medical Sciences RU
• Universidade de Santiago de Compostela ES
• Complejo Hospitalario Universitario de Santiago ES
• Wellcome Sanger Institute GB
• Radboud University Medical Center NL
• Heidelberg University DE
• Radboud University Nijmegen NL
• National University Hospital of Iceland IS

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