Disruption of the neurexin 1 gene is associated with schizophrenia

作者：Rujescu Dan; Ingason Andres; Cichon Sven; Pietilainen 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; Moeller Hans Jurgen

来源：Human Molecular Genetics, 2009, 18(5): 988-996.

DOI：10.1093/hmg/ddn351

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.

• 出版日期2009-3-1
• 单位上海市精神卫生中心