Common variants at VRK2 and TCF4 conferring risk of schizophrenia.

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)).

[1]  A. Smogorzewska,et al.  Ubiquitylation and the Fanconi anemia pathway , 2011, FEBS letters.

[2]  R. Pettinato,et al.  The Pitt‐Hopkins syndrome: Report of 16 new patients and clinical diagnostic criteria , 2011, American journal of medical genetics. Part A.

[3]  D. Rujescu,et al.  Fine mapping of ZNF804A and genome-wide significant evidence for its involvement in schizophrenia and bipolar disorder , 2011, Molecular Psychiatry.

[4]  E. Lander.  Initial impact of the sequencing of the human genome , 2011, Nature.

[5]  J. Aldenhoff,et al.  The cross-sectional GRAS sample: A comprehensive phenotypical data collection of schizophrenic patients , 2010, BMC psychiatry.

[6]  M. Rossner,et al.  Cognitive and Sensorimotor Gating Impairments in Transgenic Mice Overexpressing the Schizophrenia Susceptibility Gene Tcf4 in the Brain , 2010, Biological Psychiatry.

[7]  J. Sebat,et al.  Rare structural variants in schizophrenia: one disorder, multiple mutations; one mutation, multiple disorders. , 2009, Trends in genetics : TIG.

[8]  P. Visscher,et al.  Common polygenic variation contributes to risk of schizophrenia and bipolar disorder , 2009, Nature.

[9]  Pall I. Olason,et al.  Common variants conferring risk of schizophrenia , 2009, Nature.

[10]  Jianxin Shi,et al.  Common variants on chromosome 6p22.1 are associated with schizophrenia , 2009, Nature.

[11]  A. Munnich,et al.  Mutational, functional, and expression studies of the TCF4 gene in Pitt‐Hopkins syndrome , 2009, Human mutation.

[12]  Ryan W. Kim,et al.  Genomic Convergence Analysis of Schizophrenia: mRNA Sequencing Reveals Altered Synaptic Vesicular Transport in Post-Mortem Cerebellum , 2008, PloS one.

[13]  J. Olson,et al.  E protein dosage influences brain development more than family member identity , 2008, Journal of neuroscience research.

[14]  Claudio R. Santos,et al.  Modulation of Interleukin-1 Transcriptional Response by the Interaction between VRK2 and the JIP1 Scaffold Protein , 2008, PloS one.

[15]  A. Whitmarsh,et al.  The JIP1 Scaffold Protein Regulates Axonal Development in Cortical Neurons , 2008, Current Biology.

[16]  C. Thaller,et al.  The E-protein Tcf4 interacts with Math1 to regulate differentiation of a specific subset of neuronal progenitors , 2007, Proceedings of the National Academy of Sciences.

[17]  H. Shih,et al.  Human cellular protein VRK2 interacts specifically with Epstein-Barr virus BHRF1, a homologue of Bcl-2, and enhances cell survival. , 2006, The Journal of general virology.

[18]  P. Lazo,et al.  The subcellular localization of vaccinia‐related kinase‐2 (VRK2) isoforms determines their different effect on p53 stability in tumour cell lines , 2006, The FEBS journal.

[19]  R. Nichols,et al.  The vaccinia-related kinases phosphorylate the N' terminus of BAF, regulating its interaction with DNA and its retention in the nucleus. , 2006, Molecular biology of the cell.

[20]  C. Miller,et al.  JIP1 regulates neuronal apoptosis in response to stress. , 2005, Brain research. Molecular brain research.

[21]  Mark Gurney,et al.  The gene encoding phosphodiesterase 4D confers risk of ischemic stroke , 2003, Nature Genetics.

[22]  T. Hunter,et al.  The Protein Kinase Complement of the Human Genome , 2002, Science.

[23]  H. Axelson,et al.  HASH-1 and E2-2 are expressed in human neuroblastoma cells and form a functional complex. , 2000, Biochemical and biophysical research communications.

[24]  K. Roeder,et al.  Genomic Control for Association Studies , 1999, Biometrics.

[25]  S. K. Ray,et al.  A Splice Variant of E2–2 Basic Helix-Loop-Helix Protein Represses the Brain-specific Fibroblast Growth Factor 1 Promoter through the Binding to an Imperfect E-box* , 1998, The Journal of Biological Chemistry.

[26]  J. Nezu,et al.  Identification of two novel human putative serine/threonine kinases, VRK1 and VRK2, with structural similarity to vaccinia virus B1R kinase. , 1997, Genomics.

[27]  D. Pitt,et al.  A Syndrome of Mental Retardation, Wide Mouth and Intermittent Overbreathing , 1978, Australian paediatric journal.

[28]  J. Nurnberger,et al.  Identification of blood biomarkers for psychosis using convergent functional genomics , 2011, Molecular Psychiatry.

[29]  Informatics,et al.  E2-2 Protein and Fuchs's Corneal Dystrophy , 2022 .