Impact of DISC1 variation on neuroanatomical and neurocognitive phenotypes
Although disrupted in schizophrenia 1 (<em>DISC1</em>) has been implicated in many psychiatric disorders, including schizophrenia, bipolar disorder, schizoaffective disorder and major depression, its biological role in these disorders is unclear. To better understand this gene and its ro...
| Main Authors: | , , , , , , , , , , , , , |
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| Formato: | Journal article |
| Idioma: | English |
| Publicado: |
Nature Publishing Group
2011
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| Subjects: |
| _version_ | 1826265435974139904 |
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| author | Carless, M Glahn, D Johnson, M Curran, J Bozaoglu, K Dyer, T Winkler, A Cole, SA Almasy, L MacCluer, J Duggirala, R Moses, E Göring, H Blangero, J |
| author_facet | Carless, M Glahn, D Johnson, M Curran, J Bozaoglu, K Dyer, T Winkler, A Cole, SA Almasy, L MacCluer, J Duggirala, R Moses, E Göring, H Blangero, J |
| author_sort | Carless, M |
| collection | OXFORD |
| description | Although disrupted in schizophrenia 1 (<em>DISC1</em>) has been implicated in many psychiatric disorders, including schizophrenia, bipolar disorder, schizoaffective disorder and major depression, its biological role in these disorders is unclear. To better understand this gene and its role in psychiatric disease, we conducted transcriptional profiling and genome-wide association analysis in 1232 pedigreed Mexican-American individuals for whom we have neuroanatomic images, neurocognitive assessments and neuropsychiatric diagnoses. SOLAR was used to determine heritability, identify gene expression patterns and perform association analyses on 188 quantitative brain-related phenotypes. We found that the <em>DISC1</em> transcript is highly heritable (<em>h</em><sup>2</sup>=0.50; <em>P</em>=1.97 × 10<sup>−22</sup>), and that gene expression is strongly <em>cis</em>-regulated (<em>cis</em>-LOD=3.89) but is also influenced by <em>trans</em>-effects. We identified several <em>DISC1</em> polymorphisms that were associated with cortical gray matter thickness within the parietal, temporal and frontal lobes. Associated regions affiliated with memory included the entorhinal cortex (rs821639, <em>P</em>=4.11 × 10<sup>−5</sup>; rs2356606, <em>P</em>=4.71 × 10<sup>−4</sup>), cingulate cortex (rs16856322, <em>P</em>=2.88 × 10<sup>−4</sup>) and parahippocampal gyrus (rs821639, <em>P</em>=4.95 × 10<sup>−4</sup>); those affiliated with executive and other cognitive processing included the transverse temporal gyrus (rs9661837, <em>P</em>=5.21 × 10<sup>−4</sup>; rs17773946, <em>P</em>=6.23 × 10<sup>−4</sup>), anterior cingulate cortex (rs2487453, <em>P</em>=4.79 × 10<sup>−4</sup>; rs3738401, <em>P</em>=5.43 × 10<sup>−4</sup>) and medial orbitofrontal cortex (rs9661837; <em>P</em>=7.40 × 10<sup>−4</sup>). Cognitive measures of working memory (rs2793094, <em>P</em>=3.38 × 10<sup>−4</sup>), as well as lifetime history of depression (rs4658966, <em>P</em>=4.33 × 10<sup>−4</sup>; rs12137417, <em>P</em>=4.93 × 10<sup>−4</sup>) and panic (rs12137417, <em>P</em>=7.41 × 10<sup>−4</sup>) were associated with <em>DISC1</em> sequence variation. <em>DISC1</em> has well-defined genetic regulation and clearly influences important phenotypes related to psychiatric disease. |
| first_indexed | 2024-03-06T20:23:40Z |
| format | Journal article |
| id | oxford-uuid:2eade3a6-8b0e-4a20-913f-e212080cbd34 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T20:23:40Z |
| publishDate | 2011 |
| publisher | Nature Publishing Group |
| record_format | dspace |
| spelling | oxford-uuid:2eade3a6-8b0e-4a20-913f-e212080cbd342022-03-26T12:50:26Z Impact of DISC1 variation on neuroanatomical and neurocognitive phenotypesJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:2eade3a6-8b0e-4a20-913f-e212080cbd34Cognitive NeuroscienceNeurogeneticsAnatomyPsychiatryEnglishSymplectic Elements at OxfordNature Publishing Group2011Carless, MGlahn, DJohnson, MCurran, JBozaoglu, KDyer, TWinkler, ACole, SAAlmasy, LMacCluer, JDuggirala, RMoses, EGöring, HBlangero, JAlthough disrupted in schizophrenia 1 (<em>DISC1</em>) has been implicated in many psychiatric disorders, including schizophrenia, bipolar disorder, schizoaffective disorder and major depression, its biological role in these disorders is unclear. To better understand this gene and its role in psychiatric disease, we conducted transcriptional profiling and genome-wide association analysis in 1232 pedigreed Mexican-American individuals for whom we have neuroanatomic images, neurocognitive assessments and neuropsychiatric diagnoses. SOLAR was used to determine heritability, identify gene expression patterns and perform association analyses on 188 quantitative brain-related phenotypes. We found that the <em>DISC1</em> transcript is highly heritable (<em>h</em><sup>2</sup>=0.50; <em>P</em>=1.97 × 10<sup>−22</sup>), and that gene expression is strongly <em>cis</em>-regulated (<em>cis</em>-LOD=3.89) but is also influenced by <em>trans</em>-effects. We identified several <em>DISC1</em> polymorphisms that were associated with cortical gray matter thickness within the parietal, temporal and frontal lobes. Associated regions affiliated with memory included the entorhinal cortex (rs821639, <em>P</em>=4.11 × 10<sup>−5</sup>; rs2356606, <em>P</em>=4.71 × 10<sup>−4</sup>), cingulate cortex (rs16856322, <em>P</em>=2.88 × 10<sup>−4</sup>) and parahippocampal gyrus (rs821639, <em>P</em>=4.95 × 10<sup>−4</sup>); those affiliated with executive and other cognitive processing included the transverse temporal gyrus (rs9661837, <em>P</em>=5.21 × 10<sup>−4</sup>; rs17773946, <em>P</em>=6.23 × 10<sup>−4</sup>), anterior cingulate cortex (rs2487453, <em>P</em>=4.79 × 10<sup>−4</sup>; rs3738401, <em>P</em>=5.43 × 10<sup>−4</sup>) and medial orbitofrontal cortex (rs9661837; <em>P</em>=7.40 × 10<sup>−4</sup>). Cognitive measures of working memory (rs2793094, <em>P</em>=3.38 × 10<sup>−4</sup>), as well as lifetime history of depression (rs4658966, <em>P</em>=4.33 × 10<sup>−4</sup>; rs12137417, <em>P</em>=4.93 × 10<sup>−4</sup>) and panic (rs12137417, <em>P</em>=7.41 × 10<sup>−4</sup>) were associated with <em>DISC1</em> sequence variation. <em>DISC1</em> has well-defined genetic regulation and clearly influences important phenotypes related to psychiatric disease. |
| spellingShingle | Cognitive Neuroscience Neurogenetics Anatomy Psychiatry Carless, M Glahn, D Johnson, M Curran, J Bozaoglu, K Dyer, T Winkler, A Cole, SA Almasy, L MacCluer, J Duggirala, R Moses, E Göring, H Blangero, J Impact of DISC1 variation on neuroanatomical and neurocognitive phenotypes |
| title |
Impact of DISC1 variation on neuroanatomical and neurocognitive phenotypes |
| title_full |
Impact of DISC1 variation on neuroanatomical and neurocognitive phenotypes |
| title_fullStr |
Impact of DISC1 variation on neuroanatomical and neurocognitive phenotypes |
| title_full_unstemmed |
Impact of DISC1 variation on neuroanatomical and neurocognitive phenotypes |
| title_short |
Impact of DISC1 variation on neuroanatomical and neurocognitive phenotypes |
| title_sort | impact of disc1 variation on neuroanatomical and neurocognitive phenotypes |
| topic | Cognitive Neuroscience Neurogenetics Anatomy Psychiatry |
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