Human Molecular Genetics Advance Access published online on October 22, 2008
Human Molecular Genetics, doi:10.1093/hmg/ddn351
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Disruption of the neurexin 1 gene is associated with schizophrenia
1 Division of Molecular and Clinical Neurobiology, Department of Psychiatry, Ludwig- Maximilians-University, Munich, Germany. 2 eCODE genetics, Reykjavík, Iceland 3 Research Institute of Biological Psychiatry Mental Health Centre Sct. Hans, Copenhagen University Hospital, Roskilde, Denmark 4 Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany. 5 Institute of Human Genetics, University of Bonn, Bonn, Germany 6 Department for Molecular Medicine, National Public Health Institute, Helsinki, Finland 7 Computational Biology, GlaxoSmithKline Pharmaceuticals, Harlow, Essex, UK 8 Division of Psychological Medicine, Institute of Psychiatry, King's College, London, UK 9 Section of Psychiatry and Clinical Psychology, University of Verona, Verona, Italy 10 Department of Psychiatry, National University Hospital, Reykjavík, Iceland 11 Department of Mental Health, University of Aberdeen, Aberdeen, Scotland 12 Ravenscraig Hospital, Greenock, Scotland 13 Department of Mental Health and Addiction, National Public Health Institute, Helsinki, Finland 14 Institute of Psychiatry, University of Oslo, Oslo, Norway 15 Department of Medical Genetics, Ulleval University Hospital, Oslo, Norway 16 Dept of Epidemiology & Biostatistics (133 EPIB) / Dept of Urology (659 URO) Radboud University Nijmejen Medical Centre Nijmegen, The Netherlands 17 Department of Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands 18 Rudolf Magnus Institute of Neuroscience, Department of Psychiatry, University Medical Centre Utrecht, Utrecht, The Netherlands 19 Complex Genetics Section, DBG-Department of Medical Genetics, University Medical Centre Utrecht, Utrecht, The Netherlands 20 UCLA Center for Neurobehavioral Genetics, Los Angeles 21 Dept of Psychiatry, University Medical Centre Utrecht, Utrecht, The Netherlands 22 Dept. of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health Mannheim, University of Heidelberg, Mannheim, Germany 23 Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK 24 The Broad Institute, Cambridge, MA, USA 25 Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King's College, London, UK
* Corresponding author: David A Collier PhD Social Genetic and Developmental Psychiatry Centre, Institute of Psychiatry (King's College London), De Crespigny Park, Denmark Hill, London SE5 8AF, tel: +44 20 7848 0631, fax: +44 20 7848 0802 E-Mail: d.collier{at}iop.kcl.ac.uk
Received June 30, 2008; Revised October 17, 2008; Accepted October 17, 2008
Deletions within the neurexin 1 gene (NRXN1; 2p16.3) are associated with autism and have also been reported in two families with schizophrenia. We examined NRXN1, and the closely related NRXN2 and NRXN3 genes, for copy number variants (CNVs) in 2,977 schizophrenia patients and 33,746 controls from seven European populations (Iceland, Finland, Norway, Germany, The Netherlands, Italy and UK) using microarray data. We found 66 deletions and 5 duplications in NRXN1, including a de novo deletion: 12 deletions and 2 duplications occurred in schizophrenia cases (0.47%) compared to 49 and 3 (0.15%) in controls. There was no common breakpoint and the CNVs varied from 18kb to 420kb. No CNVs were found in NRXN2 or NRXN3. We performed a Cochran-Mantel-Haenszel exact test to estimate association between all CNVs and schizophrenia (P= 0.13; OR=1.73; 95%CI 0.81-3.50). Because the penetrance of NRXN1 CNVs may vary according to the level of functional impact on the gene, we next restricted the association analysis to CNVs that disrupt exons (0.17% of cases and 0.020% of controls). These were significantly associated with a high odds ratio (P= 0.0027; OR 8.97, 95% CI 1.8-51.9). We conclude that NRXN1 deletions affecting exons confer risk of schizophrenia.
# Note of equal contribution
GROUP investigators include; Don Linszen, René S. Kahn, Jim van Os, Durk Wiersma, Richard Bruggeman, Wiepke, Inez Germeys, Lieuwe de Haan and Lydia Krabbendam.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  M. R. Etherton, C. A. Blaiss, C. M. Powell, and T. C. Sudhof Mouse neurexin-1{alpha} deletion causes correlated electrophysiological and behavioral changes consistent with cognitive impairments PNAS, October 20, 2009; 106(42): 17998 - 18003. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. J. Williams, M. J. Owen, and M. C. O'Donovan Schizophrenia genetics: new insights from new approaches Br. Med. Bull., September 1, 2009; 91(1): 61 - 74. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Kirov, D. Rujescu, A. Ingason, D. A. Collier, M. C. O'Donovan, and M. J. Owen Neurexin 1 (NRXN1) Deletions in Schizophrenia Schizophr Bull, September 1, 2009; 35(5): 851 - 854. [Full Text] [PDF]
|
|