A common variant in the 3'UTR of the GRIK4 glutamate receptor gene affects transcript abundance and protects against bipolar disorder.
Underactivity of the glutamatergic system is an attractive model for the pathophysiology of several major mental illnesses. We previously described a chromosome abnormality disrupting the kainate class ionotropic glutamate receptor gene, GRIK4/KA1, in an individual with schizophrenia and learning di...
| Những tác giả chính: | , , , , , , , , , , , , , , |
|---|---|
| Định dạng: | Journal article |
| Ngôn ngữ: | English |
| Được phát hành: |
2008
|
| _version_ | 1826272265988210688 |
|---|---|
| author | Pickard, B Knight, H Hamilton, R Soares, D Walker, R Boyd, J Machell, J Maclean, A McGhee, K Condie, A Porteous, D St Clair, D Davis, I Blackwood, D Muir, W |
| author_facet | Pickard, B Knight, H Hamilton, R Soares, D Walker, R Boyd, J Machell, J Maclean, A McGhee, K Condie, A Porteous, D St Clair, D Davis, I Blackwood, D Muir, W |
| author_sort | Pickard, B |
| collection | OXFORD |
| description | Underactivity of the glutamatergic system is an attractive model for the pathophysiology of several major mental illnesses. We previously described a chromosome abnormality disrupting the kainate class ionotropic glutamate receptor gene, GRIK4/KA1, in an individual with schizophrenia and learning disability (mental retardation). We also demonstrated in a case-control study that two physically separated haplotypes within this gene were significantly associated with increased risk of schizophrenia and decreased risk of bipolar disorder, respectively. The latter protective haplotype was located at the 3' end of the gene. We now report the identification from carriers of the protective haplotype of a deletion variant within the 3' untranslated region of the gene. The deletion allele also was found to be negatively associated with bipolar disorder in both initial (P = 0.00000019) and replication (P = 0.0107) case-control studies. Expression studies indicated that deletion-carrying mRNA transcripts were relatively more abundant. We postulate that this may be a direct consequence of the differences in the RNA secondary structures predicted for the insertion and deletion alleles. These data suggest a mechanism whereby the genetic protective effect is mediated through increased kainate receptor expression. |
| first_indexed | 2024-03-06T22:09:50Z |
| format | Journal article |
| id | oxford-uuid:516db0d7-c255-4118-bbc9-f401e1b70f8d |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T22:09:50Z |
| publishDate | 2008 |
| record_format | dspace |
| spelling | oxford-uuid:516db0d7-c255-4118-bbc9-f401e1b70f8d2022-03-26T16:19:30ZA common variant in the 3'UTR of the GRIK4 glutamate receptor gene affects transcript abundance and protects against bipolar disorder.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:516db0d7-c255-4118-bbc9-f401e1b70f8dEnglishSymplectic Elements at Oxford2008Pickard, BKnight, HHamilton, RSoares, DWalker, RBoyd, JMachell, JMaclean, AMcGhee, KCondie, APorteous, DSt Clair, DDavis, IBlackwood, DMuir, WUnderactivity of the glutamatergic system is an attractive model for the pathophysiology of several major mental illnesses. We previously described a chromosome abnormality disrupting the kainate class ionotropic glutamate receptor gene, GRIK4/KA1, in an individual with schizophrenia and learning disability (mental retardation). We also demonstrated in a case-control study that two physically separated haplotypes within this gene were significantly associated with increased risk of schizophrenia and decreased risk of bipolar disorder, respectively. The latter protective haplotype was located at the 3' end of the gene. We now report the identification from carriers of the protective haplotype of a deletion variant within the 3' untranslated region of the gene. The deletion allele also was found to be negatively associated with bipolar disorder in both initial (P = 0.00000019) and replication (P = 0.0107) case-control studies. Expression studies indicated that deletion-carrying mRNA transcripts were relatively more abundant. We postulate that this may be a direct consequence of the differences in the RNA secondary structures predicted for the insertion and deletion alleles. These data suggest a mechanism whereby the genetic protective effect is mediated through increased kainate receptor expression. |
| spellingShingle | Pickard, B Knight, H Hamilton, R Soares, D Walker, R Boyd, J Machell, J Maclean, A McGhee, K Condie, A Porteous, D St Clair, D Davis, I Blackwood, D Muir, W A common variant in the 3'UTR of the GRIK4 glutamate receptor gene affects transcript abundance and protects against bipolar disorder. |
| title | A common variant in the 3'UTR of the GRIK4 glutamate receptor gene affects transcript abundance and protects against bipolar disorder. |
| title_full | A common variant in the 3'UTR of the GRIK4 glutamate receptor gene affects transcript abundance and protects against bipolar disorder. |
| title_fullStr | A common variant in the 3'UTR of the GRIK4 glutamate receptor gene affects transcript abundance and protects against bipolar disorder. |
| title_full_unstemmed | A common variant in the 3'UTR of the GRIK4 glutamate receptor gene affects transcript abundance and protects against bipolar disorder. |
| title_short | A common variant in the 3'UTR of the GRIK4 glutamate receptor gene affects transcript abundance and protects against bipolar disorder. |
| title_sort | common variant in the 3 utr of the grik4 glutamate receptor gene affects transcript abundance and protects against bipolar disorder |
| work_keys_str_mv | AT pickardb acommonvariantinthe3utrofthegrik4glutamatereceptorgeneaffectstranscriptabundanceandprotectsagainstbipolardisorder AT knighth acommonvariantinthe3utrofthegrik4glutamatereceptorgeneaffectstranscriptabundanceandprotectsagainstbipolardisorder AT hamiltonr acommonvariantinthe3utrofthegrik4glutamatereceptorgeneaffectstranscriptabundanceandprotectsagainstbipolardisorder AT soaresd acommonvariantinthe3utrofthegrik4glutamatereceptorgeneaffectstranscriptabundanceandprotectsagainstbipolardisorder AT walkerr acommonvariantinthe3utrofthegrik4glutamatereceptorgeneaffectstranscriptabundanceandprotectsagainstbipolardisorder AT boydj acommonvariantinthe3utrofthegrik4glutamatereceptorgeneaffectstranscriptabundanceandprotectsagainstbipolardisorder AT machellj acommonvariantinthe3utrofthegrik4glutamatereceptorgeneaffectstranscriptabundanceandprotectsagainstbipolardisorder AT macleana acommonvariantinthe3utrofthegrik4glutamatereceptorgeneaffectstranscriptabundanceandprotectsagainstbipolardisorder AT mcgheek acommonvariantinthe3utrofthegrik4glutamatereceptorgeneaffectstranscriptabundanceandprotectsagainstbipolardisorder AT condiea acommonvariantinthe3utrofthegrik4glutamatereceptorgeneaffectstranscriptabundanceandprotectsagainstbipolardisorder AT porteousd acommonvariantinthe3utrofthegrik4glutamatereceptorgeneaffectstranscriptabundanceandprotectsagainstbipolardisorder AT stclaird acommonvariantinthe3utrofthegrik4glutamatereceptorgeneaffectstranscriptabundanceandprotectsagainstbipolardisorder AT davisi acommonvariantinthe3utrofthegrik4glutamatereceptorgeneaffectstranscriptabundanceandprotectsagainstbipolardisorder AT blackwoodd acommonvariantinthe3utrofthegrik4glutamatereceptorgeneaffectstranscriptabundanceandprotectsagainstbipolardisorder AT muirw acommonvariantinthe3utrofthegrik4glutamatereceptorgeneaffectstranscriptabundanceandprotectsagainstbipolardisorder AT pickardb commonvariantinthe3utrofthegrik4glutamatereceptorgeneaffectstranscriptabundanceandprotectsagainstbipolardisorder AT knighth commonvariantinthe3utrofthegrik4glutamatereceptorgeneaffectstranscriptabundanceandprotectsagainstbipolardisorder AT hamiltonr commonvariantinthe3utrofthegrik4glutamatereceptorgeneaffectstranscriptabundanceandprotectsagainstbipolardisorder AT soaresd commonvariantinthe3utrofthegrik4glutamatereceptorgeneaffectstranscriptabundanceandprotectsagainstbipolardisorder AT walkerr commonvariantinthe3utrofthegrik4glutamatereceptorgeneaffectstranscriptabundanceandprotectsagainstbipolardisorder AT boydj commonvariantinthe3utrofthegrik4glutamatereceptorgeneaffectstranscriptabundanceandprotectsagainstbipolardisorder AT machellj commonvariantinthe3utrofthegrik4glutamatereceptorgeneaffectstranscriptabundanceandprotectsagainstbipolardisorder AT macleana commonvariantinthe3utrofthegrik4glutamatereceptorgeneaffectstranscriptabundanceandprotectsagainstbipolardisorder AT mcgheek commonvariantinthe3utrofthegrik4glutamatereceptorgeneaffectstranscriptabundanceandprotectsagainstbipolardisorder AT condiea commonvariantinthe3utrofthegrik4glutamatereceptorgeneaffectstranscriptabundanceandprotectsagainstbipolardisorder AT porteousd commonvariantinthe3utrofthegrik4glutamatereceptorgeneaffectstranscriptabundanceandprotectsagainstbipolardisorder AT stclaird commonvariantinthe3utrofthegrik4glutamatereceptorgeneaffectstranscriptabundanceandprotectsagainstbipolardisorder AT davisi commonvariantinthe3utrofthegrik4glutamatereceptorgeneaffectstranscriptabundanceandprotectsagainstbipolardisorder AT blackwoodd commonvariantinthe3utrofthegrik4glutamatereceptorgeneaffectstranscriptabundanceandprotectsagainstbipolardisorder AT muirw commonvariantinthe3utrofthegrik4glutamatereceptorgeneaffectstranscriptabundanceandprotectsagainstbipolardisorder |