Abstract
| Original language | English |
|---|---|
| Pages (from-to) | 988-996 |
| Number of pages | 9 |
| Journal | Human Molecular Genetics |
| Volume | 18 |
| Issue number | 5 |
| Early online date | 22 Oct 2008 |
| DOIs | |
| Publication status | Published - 2009 |
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Keywords
- adolescent
- adult
- case-control studies
- European continental ancestry group
- exons
- female
- gene deletion
- gene dosage
- gene duplication
- gene silencing
- genetic predisposition to disease
- humans
- male
- nerve tissue proteins
- schizophrenia
- young adult
Cite this
Disruption of the neurexin 1 gene is associated with schizophrenia. / Rujescu, Dan; Ingason, Andres; Cichon, Sven; Pietiläinen, Olli P H; Barnes, Michael R. ; Toulopoulou, Timothea; Picchioni, Marco; Vassos, Evangelos; Ettinger, Ulrich; Bramon, Elvira; Murray, Robin; Ruggeri, Mirella; Tosato, Sarah; Bonetto, Chiara; Steinberg, Stacy; Sigurdsson, Engilbert; Sigmundsson, Thordur; Petursson, Hannes; Gylfason, Arnaldur; Olason, Pall I; Hardarsson, Gudmundur; Jonsdottir, Gudrun A; Gustafsson, Omar; Fossdal, Ragnheidur; Giegling, Ina; Möller, Hans-Jürgen; Hartmann, Annette M; Hoffmann, Per; Crombie, Caroline; Fraser, Gillian; Walker, Nicholas; Lonnqvist, Jouko; Suvisaari, Jaana; Tuulio-Henriksson, Annamari; Djurovic, Srdjan; Melle, Ingrid; Andreassen, Ole A; Hansen, Thomas; Werge, Thomas; Kiemeney, Lambertus A; Franke, Barbara; Veltman, Joris; Buizer-Voskamp, Jacobine E; Sabatti, Chiara; Ophoff, Roel A; Rietschel, Marcella; Nöthen, Markus M; Stefansson, Kari; Peltonen, Leena; St Clair, David; GROUP Investigators.
In: Human Molecular Genetics, Vol. 18, No. 5, 2009, p. 988-996.Research output: Contribution to journal › Article
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TY - JOUR
T1 - Disruption of the neurexin 1 gene is associated with schizophrenia
AU - Rujescu, Dan
AU - Ingason, Andres
AU - Cichon, Sven
AU - Pietiläinen, Olli P H
AU - Barnes, Michael R.
AU - Toulopoulou, Timothea
AU - Picchioni, Marco
AU - Vassos, Evangelos
AU - Ettinger, Ulrich
AU - Bramon, Elvira
AU - Murray, Robin
AU - Ruggeri, Mirella
AU - Tosato, Sarah
AU - Bonetto, Chiara
AU - Steinberg, Stacy
AU - Sigurdsson, Engilbert
AU - Sigmundsson, Thordur
AU - Petursson, Hannes
AU - Gylfason, Arnaldur
AU - Olason, Pall I
AU - Hardarsson, Gudmundur
AU - Jonsdottir, Gudrun A
AU - Gustafsson, Omar
AU - Fossdal, Ragnheidur
AU - Giegling, Ina
AU - Möller, Hans-Jürgen
AU - Hartmann, Annette M
AU - Hoffmann, Per
AU - Crombie, Caroline
AU - Fraser, Gillian
AU - Walker, Nicholas
AU - Lonnqvist, Jouko
AU - Suvisaari, Jaana
AU - Tuulio-Henriksson, Annamari
AU - Djurovic, Srdjan
AU - Melle, Ingrid
AU - Andreassen, Ole A
AU - Hansen, Thomas
AU - Werge, Thomas
AU - Kiemeney, Lambertus A
AU - Franke, Barbara
AU - Veltman, Joris
AU - Buizer-Voskamp, Jacobine E
AU - Sabatti, Chiara
AU - Ophoff, Roel A
AU - Rietschel, Marcella
AU - Nöthen, Markus M
AU - Stefansson, Kari
AU - Peltonen, Leena
AU - St Clair, David
AU - GROUP Investigators
PY - 2009
Y1 - 2009
N2 - 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 2977 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 18 to 420 kb. 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 (0.24% of cases and 0.015% 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.
AB - 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 2977 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 18 to 420 kb. 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 (0.24% of cases and 0.015% 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.
KW - adolescent
KW - adult
KW - case-control studies
KW - European continental ancestry group
KW - exons
KW - female
KW - gene deletion
KW - gene dosage
KW - gene duplication
KW - gene silencing
KW - genetic predisposition to disease
KW - humans
KW - male
KW - nerve tissue proteins
KW - schizophrenia
KW - young adult
U2 - 10.1093/hmg/ddn351
DO - 10.1093/hmg/ddn351
M3 - Article
C2 - 18945720
VL - 18
SP - 988
EP - 996
JO - Human Molecular Genetics
JF - Human Molecular Genetics
SN - 0964-6906
IS - 5
ER -