The DTNBP1 (Dysbindin) Gene Contributes to Schizophrenia, Depending on Family History of the Disease

Ann Van Den Bogaert, Johannes Schumacher, Thomas G. Schulze, Andreas C. Otte, Stephanie Ohlraun, Svetlana Kovalenko, Tim Becker, Jan Freudenberg, Erik G. Jönsson, Marja Mattila-Evenden, Göran C. Sedvall, Piotr M. Czerski, Pawel Kapelski, Joanna Hauser, Wolfgang Maier, Marcella Rietschel, Peter Propping, Markus M. Nöthen, Sven Cichon

Research output: Contribution to journalArticlepeer-review

169 Scopus citations


We have investigated the gene for dystrobrevin-binding protein 1 (DTNBP1), or dysbindin, which has been strongly suggested as a positional candidate gene for schizophrenia, in three samples of subjects with schizophrenia and unaffected control subjects of German (418 cases, 285 controls), Polish (294 cases, 113 controls), and Swedish (142 cases, 272 controls) descent. We analyzed five single-nucleotide polymorphisms (P1635, P1325, P1320, P1757, and P1578) and identified significant evidence of association in the Swedish sample but not in those from Germany or Poland. The results in the Swedish sample became even more significant after a separate analysis of those cases with a positive family history of schizophrenia, in whom the five-marker haplotype A-C-A-T-T showed a P value of .00009 (3.1% in controls, 17.8% in cases; OR 6. 75; P = .00153 after Bonferroni correction). Our results suggest that genetic variation in the dysbindin gene is particularly involved in the development of schizophrenia in cases with a familial loading of the disease. This would also explain the difficulty of replicating this association in consecutively ascertained case-control samples, which usually comprise only a small proportion of subjects with a family history of disease.

Original languageEnglish (US)
Pages (from-to)1438-1443
Number of pages6
JournalAmerican Journal of Human Genetics
Issue number6
StatePublished - Dec 2003
Externally publishedYes

ASJC Scopus subject areas

  • Genetics


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