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Investigation of the role of TCF4 rare sequence variants in schizophrenia

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DOI

  • F Buket Basmanav, Institute of Human Genetics, University of Bonn, Bonn, Germany Department of Neonatology, University of Bonn, Bonn, Germany., Germany
  • Andreas J Forstner, Institute of Human Genetics, University of Bonn, Bonn, Germany Department of Neonatology, University of Bonn, Bonn, Germany., Germany
  • Heide Fier, Institute of Human Genetics, University of Bonn, Bonn, Germany Department of Neonatology, University of Bonn, Bonn, Germany., Germany
  • Stefan Herms, Department of Genomics, Life and Brain Center,Institute of Human Genetics, and., Germany
  • Sandra Meier
  • ,
  • Franziska Degenhardt, Institute of Human Genetics, University of Bonn, Bonn, Germany Department of Neonatology, University of Bonn, Bonn, Germany., Germany
  • Per Hoffmann, Institute of Human Genetics, University of Bonn, Bonn, Germany Department of Neonatology, University of Bonn, Bonn, Germany., Germany
  • Sandra Barth, Institute of Human Genetics, University of Bonn, Bonn, Germany Department of Neonatology, University of Bonn, Bonn, Germany., Germany
  • Nadine Fricker, Institute of Human Genetics, University of Bonn, Bonn, Germany Department of Neonatology, University of Bonn, Bonn, Germany., Germany
  • Jana Strohmaier, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
  • Stephanie H Witt, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
  • Michael Ludwig, University of Bonn, Germany
  • Christine Schmael, Institute of Human Genetics, University of Bonn, Bonn, Germany Department of Neonatology, University of Bonn, Bonn, Germany., Germany
  • Susanne Moebus, Centre of Urban Epidemiology, Institute of Medical Informatics, Biometry and Epidemiology, Essen, Germany
  • Wolfgang Maier, Department of Psychiatry, University of Bonn, D-53127 Bonn, Germany., Germany
  • Rainald Mössner, Univ Bonn, University of Bonn, Dept Psychiat, Germany
  • Dan Rujescu, The Department of Psychiatry, University of Halle-Wittenberg, Halle, Germany., Germany
  • Marcella Rietschel, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
  • Christoph Lange, University of Bonn, Germany
  • Markus M Nöthen, Institute of Human Genetics, University of Bonn, Bonn, Germany Department of Neonatology, University of Bonn, Bonn, Germany., Germany
  • Sven Cichon, Institute of Human Genetics, University of Bonn, Bonn, Germany Department of Neonatology, University of Bonn, Bonn, Germany., Germany

Transcription factor 4 (TCF4) is one of the most robust of all reported schizophrenia risk loci and is supported by several genetic and functional lines of evidence. While numerous studies have implicated common genetic variation at TCF4 in schizophrenia risk, the role of rare, small-sized variants at this locus-such as single nucleotide variants and short indels which are below the resolution of chip-based arrays requires further exploration. The aim of the present study was to investigate the association between rare TCF4 sequence variants and schizophrenia. Exon-targeted resequencing was performed in 190 German schizophrenia patients. Six rare variants at the coding exons and flanking sequences of the TCF4 gene were identified, including two missense variants and one splice site variant. These six variants were then pooled with nine additional rare variants identified in 379 European participants of the 1000 Genomes Project, and all 15 variants were genotyped in an independent German sample (n = 1,808 patients; n = 2,261 controls). These data were then analyzed using six statistical methods developed for the association analysis of rare variants. No significant association (P < 0.05) was found. However, the results from our association and power analyses suggest that further research into the possible involvement of rare TCF4 sequence variants in schizophrenia risk is warranted by the assessment of larger cohorts with higher statistical power to identify rare variant associations.

Original languageEnglish
JournalAmerican journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics
Volume168B
Issue5
Pages (from-to)354-362
Number of pages9
ISSN1552-4841
DOIs
Publication statusPublished - Jul 2015

    Research areas

  • Transcription factor 4, Rare variants, Resequencing, Schizophrenia, Neurodevelopmental disorder

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