Disruption of the neurexin 1 gene is associated with schizophrenia.

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.

journal_name

Hum Mol Genet

journal_title

Human molecular genetics

authors

Rujescu D,Ingason A,Cichon S,Pietiläinen OP,Barnes MR,Toulopoulou T,Picchioni M,Vassos E,Ettinger U,Bramon E,Murray R,Ruggeri M,Tosato S,Bonetto C,Steinberg S,Sigurdsson E,Sigmundsson T,Petursson H,Gylfason A,Olason

doi

10.1093/hmg/ddn351

subject

Has Abstract

pub_date

2009-03-01 00:00:00

pages

988-96

issue

5

eissn

0964-6906

issn

1460-2083

pii

ddn351

journal_volume

18

pub_type

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