A reappraisal of the association between Dysbindin (DTNBP1) and schizophrenia in a large combined case–control and family-based sample of German ancestry

Strohmaier, Jana; Frank, Josef; Wendland, Jens R.; Schumacher, Johannes; Jamra, Rami Abou; Treutlein, Jens; Nieratschker, Vanessa; Breuer, René; Mattheisen, Manuel; Herms, Stefan; Mühleisen, Thomas W.; Maier, Wolfgang; Nöthen, Markus M.; Cichon, Sven; Rietschel, Marcella; Schulze, Thomas G.

doi:10.1016/j.schres.2009.12.025

« Previous Next »Schizophrenia Research
Volume 118, Issue 1 , Pages 98-105, May 2010

A reappraisal of the association between Dysbindin (DTNBP1) and schizophrenia in a large combined case–control and family-based sample of German ancestry

Jana Strohmaier
- Division of Genetic Epidemiology, Central Institute of Mental Health, Mannheim, Germany
Josef Frank
- Division of Genetic Epidemiology, Central Institute of Mental Health, Mannheim, Germany
Jens R. Wendland
- Unit on the Genetic Basis of Mood and Anxiety Disorders, NIMH, NIH, Bethesda, USA
Johannes Schumacher
- Unit on the Genetic Basis of Mood and Anxiety Disorders, NIMH, NIH, Bethesda, USA
- Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany
Rami Abou Jamra
- Institute of Human Genetics, University of Bonn, Bonn, Germany
Jens Treutlein
- Division of Genetic Epidemiology, Central Institute of Mental Health, Mannheim, Germany
Vanessa Nieratschker
- Division of Genetic Epidemiology, Central Institute of Mental Health, Mannheim, Germany
René Breuer
- Division of Genetic Epidemiology, Central Institute of Mental Health, Mannheim, Germany
Manuel Mattheisen
- Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany
- Institute of Human Genetics, University of Bonn, Bonn, Germany
Stefan Herms
- Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany
- Institute of Human Genetics, University of Bonn, Bonn, Germany
Thomas W. Mühleisen
- Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany
- Institute of Human Genetics, University of Bonn, Bonn, Germany
Wolfgang Maier
- Department of Psychiatry and Psychotherapy, University of Bonn, Bonn, Germany
Markus M. Nöthen
- Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany
- Institute of Human Genetics, University of Bonn, Bonn, Germany
Sven Cichon
- Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany
- Institute of Human Genetics, University of Bonn, Bonn, Germany
Marcella Rietschel
- Division of Genetic Epidemiology, Central Institute of Mental Health, Mannheim, Germany
Thomas G. Schulze
- Division of Genetic Epidemiology, Central Institute of Mental Health, Mannheim, Germany
- Unit on the Genetic Basis of Mood and Anxiety Disorders, NIMH, NIH, Bethesda, USA
- Corresponding author. Unit on the Genetic Basis of Mood and Anxiety Disorders, National Institute of Mental Health (NIMH), National Institutes of Health (NIH), 35 Convent Drive, Bldg. 35, Rm 1A205, MSC 3719, Bethesda, MD 20892-3719, USA. Tel.: +1 301 451 7213; fax: +1 301 402 9081.

Received 19 August 2009; received in revised form 8 December 2009; accepted 20 December 2009. published online 18 January 2010.

Abstract

Background

Dysbindin (DTNBP1) is a widely studied candidate gene for schizophrenia (SCZ); however, inconsistent results across studies triggered skepticism towards the validity of the findings. In this HapMap-based study, we reappraised the association between Dysbindin and SCZ in a large sample of German ethnicity.

Method

Six hundred thirty-four cases with DSM-IV SCZ, 776 controls, and 180 parent–offspring trios were genotyped for 38 Dysbindin SNPs. We also studied two phenotypically-defined subsamples: 147 patients with a positive family history of SCZ (FH-SCZ+) and SCZ patients characterized for cognitive performance with Trail-Making Tests A and B (TMT-A: n=219; TMT-B: n=247). Given previous evidence of gene–gene interactions in SCZ involving the COMT gene, we also assessed epistatic interactions between Dysbindin markers and 14 SNPs in COMT.

Results

No association was detected between Dysbindin markers and SCZ, or in the FH-SCZ+ subgroup. Only one marker (rs1047631, previously reported to be part of a risk haplotype), showed a nominally significant association with performance on TMT-A and TMT-B; these findings did not remain significant after correction for multiple comparisons. Similarly, no pair-wise epistatic interactions between Dysbindin and COMT markers remained significant after correction for 504 pair-wise comparisons.

Conclusions

Our results, based on one of the largest samples of European Caucasians and using narrowly-defined criteria for SCZ, do not support the etiological involvement of Dysbindin markers in SCZ. Larger samples may be needed in order to unravel Dysbindin's possible role in the genetic basis of proposed intermediate phenotypes of SCZ or to detect epistatic interactions.

Keywords: Polymorphism, COMT, Epistasis, Endophenotype, Cognitive function