Disruption of the neurexin 1 gene is associated with schizophrenia. Export

@article{citeulike:3459843, abstract = {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.}, author = {Rujescu, Dan and Ingason, Andres and Cichon, Sven and Pietil\"{a}inen, Olli P. and Barnes, Michael R. and Toulopoulou, Timothea and Picchioni, Marco and Vassos, Evangelos and Ettinger, Ulrich and Bramon, Elvira and Murray, Robin and Ruggeri, Mirella and Tosato, Sarah and Bonetto, Chiara and Steinberg, Stacy and Sigurdsson, Engilbert and Sigmundsson, Thordur and Petursson, Hannes and Gylfason, Arnaldur and Olason, Pall I. and Hardarsson, Gudmundur and Jonsdottir, Gudrun A. and Gustafsson, Omar and Fossdal, Ragnheidur and Giegling, Ina and M\"{o}ller, Hans-J\"{u}rgen J. and Hartmann, Annette M. and Hoffmann, Per and Crombie, Caroline and Fraser, Gillian and Walker, Nicholas and Lonnqvist, Jouko and Suvisaari, Jaana and Tuulio-Henriksson, Annamari and Djurovic, Srdjan and Melle, Ingrid and Andreassen, Ole A. and Hansen, Thomas and Werge, Thomas and Kiemeney, Lambertus A. and Franke, Barbara and Veltman, Joris and Buizer-Voskamp, Jacobine E. and {GROUP Investigators} and Sabatti, Chiara and Ophoff, Roel A. and Rietschel, Marcella and N\"{o}then, Markus M. and Stefansson, Kari and Peltonen, Leena and St Clair, David and Stefansson, Hreinn and Collier, David A.}, citeulike-article-id = {3459843}, citeulike-linkout-0 = {http://dx.doi.org/10.1093/hmg/ddn351}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/18945720}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=18945720}, day = {1}, doi = {10.1093/hmg/ddn351}, issn = {1460-2083}, journal = {Human molecular genetics}, keywords = {association, nrxn1, schizophrenia}, month = {March}, number = {5}, pages = {988--996}, posted-at = {2009-10-30 16:33:26}, priority = {2}, title = {Disruption of the neurexin 1 gene is associated with schizophrenia.}, url = {http://dx.doi.org/10.1093/hmg/ddn351}, volume = {18}, year = {2009} }

TY - JOUR ID - citeulike:3459843 L3 - citeulike-article-id:3459843 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. IS - 5 JF - Human molecular genetics SN - 1460-2083 EP - 996 TI - Disruption of the neurexin 1 gene is associated with schizophrenia. VL - 18 SP - 988 KW - association KW - nrxn1 KW - schizophrenia AU - Rujescu, Dan AU - Ingason, Andres AU - Cichon, Sven AU - Pietiläinen, Olli AU - Barnes, Michael 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 AU - Hardarsson, Gudmundur AU - Jonsdottir, Gudrun AU - Gustafsson, Omar AU - Fossdal, Ragnheidur AU - Giegling, Ina AU - Möller, Hans-Jürgen AU - Hartmann, Annette 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 AU - Hansen, Thomas AU - Werge, Thomas AU - Kiemeney, Lambertus AU - Franke, Barbara AU - Veltman, Joris AU - Buizer-Voskamp, Jacobine AU - Sabatti, Chiara AU - Ophoff, Roel AU - Rietschel, Marcella AU - Nöthen, Markus AU - Stefansson, Kari AU - Peltonen, Leena AU - St Clair, David AU - Stefansson, Hreinn AU - Collier, David PY - 2009/03/01/ UR - http://dx.doi.org/10.1093/hmg/ddn351 ER -