Neurexin-1 and frontal lobe white matter: an overlapping intermediate phenotype for schizophrenia and autism spectrum disorders.
Structural variation in the neurexin-1 (NRXN1) gene increases risk for both autism spectrum disorders (ASD) and schizophrenia. However, the manner in which NRXN1 gene variation may be related to brain morphology to confer risk for ASD or schizophrenia is unknown.53 healthy individuals between 18-59...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2011-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3110800?pdf=render |
| _version_ | 1818136385627881472 |
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| author | Aristotle N Voineskos Tristram A P Lett Jason P Lerch Arun K Tiwari Stephanie H Ameis Tarek K Rajji Daniel J Müller Benoit H Mulsant James L Kennedy |
| author_facet | Aristotle N Voineskos Tristram A P Lett Jason P Lerch Arun K Tiwari Stephanie H Ameis Tarek K Rajji Daniel J Müller Benoit H Mulsant James L Kennedy |
| author_sort | Aristotle N Voineskos |
| collection | DOAJ |
| description | Structural variation in the neurexin-1 (NRXN1) gene increases risk for both autism spectrum disorders (ASD) and schizophrenia. However, the manner in which NRXN1 gene variation may be related to brain morphology to confer risk for ASD or schizophrenia is unknown.53 healthy individuals between 18-59 years of age were genotyped at 11 single nucleotide polymorphisms of the NRXN1 gene. All subjects received structural MRI scans, which were processed to determine cortical gray and white matter lobar volumes, and volumes of striatal and thalamic structures. Each subject's sensorimotor function was also assessed. The general linear model was used to calculate the influence of genetic variation on neural and cognitive phenotypes. Finally, in silico analysis was conducted to assess potential functional relevance of any polymorphisms associated with brain measures. A polymorphism located in the 3' untranslated region of NRXN1 significantly influenced white matter volumes in whole brain and frontal lobes after correcting for total brain volume, age and multiple comparisons. Follow-up in silico analysis revealed that this SNP is a putative microRNA binding site that may be of functional significance in regulating NRXN1 expression. This variant also influenced sensorimotor performance, a neurocognitive function impaired in both ASD and schizophrenia.Our findings demonstrate that the NRXN1 gene, a vulnerability gene for SCZ and ASD, influences brain structure and cognitive function susceptible in both disorders. In conjunction with our in silico results, our findings provide evidence for a neural and cognitive susceptibility mechanism by which the NRXN1 gene confers risk for both schizophrenia and ASD. |
| first_indexed | 2024-12-11T09:39:34Z |
| format | Article |
| id | doaj.art-2381d258e5e54d3b9e1537f9615033f1 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-11T09:39:34Z |
| publishDate | 2011-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-2381d258e5e54d3b9e1537f9615033f12022-12-22T01:12:42ZengPublic Library of Science (PLoS)PLoS ONE1932-62032011-01-0166e2098210.1371/journal.pone.0020982Neurexin-1 and frontal lobe white matter: an overlapping intermediate phenotype for schizophrenia and autism spectrum disorders.Aristotle N VoineskosTristram A P LettJason P LerchArun K TiwariStephanie H AmeisTarek K RajjiDaniel J MüllerBenoit H MulsantJames L KennedyStructural variation in the neurexin-1 (NRXN1) gene increases risk for both autism spectrum disorders (ASD) and schizophrenia. However, the manner in which NRXN1 gene variation may be related to brain morphology to confer risk for ASD or schizophrenia is unknown.53 healthy individuals between 18-59 years of age were genotyped at 11 single nucleotide polymorphisms of the NRXN1 gene. All subjects received structural MRI scans, which were processed to determine cortical gray and white matter lobar volumes, and volumes of striatal and thalamic structures. Each subject's sensorimotor function was also assessed. The general linear model was used to calculate the influence of genetic variation on neural and cognitive phenotypes. Finally, in silico analysis was conducted to assess potential functional relevance of any polymorphisms associated with brain measures. A polymorphism located in the 3' untranslated region of NRXN1 significantly influenced white matter volumes in whole brain and frontal lobes after correcting for total brain volume, age and multiple comparisons. Follow-up in silico analysis revealed that this SNP is a putative microRNA binding site that may be of functional significance in regulating NRXN1 expression. This variant also influenced sensorimotor performance, a neurocognitive function impaired in both ASD and schizophrenia.Our findings demonstrate that the NRXN1 gene, a vulnerability gene for SCZ and ASD, influences brain structure and cognitive function susceptible in both disorders. In conjunction with our in silico results, our findings provide evidence for a neural and cognitive susceptibility mechanism by which the NRXN1 gene confers risk for both schizophrenia and ASD.http://europepmc.org/articles/PMC3110800?pdf=render |
| spellingShingle | Aristotle N Voineskos Tristram A P Lett Jason P Lerch Arun K Tiwari Stephanie H Ameis Tarek K Rajji Daniel J Müller Benoit H Mulsant James L Kennedy Neurexin-1 and frontal lobe white matter: an overlapping intermediate phenotype for schizophrenia and autism spectrum disorders. PLoS ONE |
| title | Neurexin-1 and frontal lobe white matter: an overlapping intermediate phenotype for schizophrenia and autism spectrum disorders. |
| title_full | Neurexin-1 and frontal lobe white matter: an overlapping intermediate phenotype for schizophrenia and autism spectrum disorders. |
| title_fullStr | Neurexin-1 and frontal lobe white matter: an overlapping intermediate phenotype for schizophrenia and autism spectrum disorders. |
| title_full_unstemmed | Neurexin-1 and frontal lobe white matter: an overlapping intermediate phenotype for schizophrenia and autism spectrum disorders. |
| title_short | Neurexin-1 and frontal lobe white matter: an overlapping intermediate phenotype for schizophrenia and autism spectrum disorders. |
| title_sort | neurexin 1 and frontal lobe white matter an overlapping intermediate phenotype for schizophrenia and autism spectrum disorders |
| url | http://europepmc.org/articles/PMC3110800?pdf=render |
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