Fiorentino, A;
Sharp, SI;
McQuillin, A;
(2015)
Association of rare variation in the glutamate receptor gene SLC1A2 with susceptibility to bipolar disorder and schizophrenia.
European Journal of Human Genetics
, 23
pp. 1200-1206.
10.1038/ejhg.2014.261.
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Abstract
The SLC1A2 gene encodes the excitatory amino acid transporter 2 (EAAT2). Glutamate is the major mediator of excitatory neurotransmission and EAAT2 is responsible for clearing the neurotransmitter from the synaptic cleft. Genetic variation in SLC1A2 has been implicated in a range of neurological and neuropsychiatric conditions including schizophrenia (SZ), autism and in core phenotypes of bipolar disorder (BD). The coding and putative regulatory regions of SLC1A2 gene were screened for variants using high resolution melting or sequenced in 1,099 or in 32 BD subjects respectively. Thirty-two variants were detected in the SLC1A2 gene. Fifteen potentially etiological variants were selected for genotyping in 1,099 BD and 1,095 control samples. Five amino acid changing variants were also genotyped in 630 participants suffering from SZ. None of the variants were found to be associated with BD or SZ or with the two diseases combined. However, two recurrent missense variants (rs145827578:G>A, p.(G6S); rs199599866:G>A, p.(R31Q)) and one recurrent 5’ untranslated region variant (ss825678885:G>T) were detected in cases only. Combined analysis of the recurrent case only missense variants and of the case only missense and 5’ untranslated region variants showed nominal evidence for association with the combined diseases (Fisher’s P= 0.019 and 0.0076). These findings are exploratory in nature and await replication in larger cohorts, however they provide intriguing evidence that potentially functional rare variants in the SLC1A2 gene may harbour susceptibility to psychotic disorders.
| Type: | Article |
|---|---|
| Title: | Association of rare variation in the glutamate receptor gene SLC1A2 with susceptibility to bipolar disorder and schizophrenia |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1038/ejhg.2014.261 |
| Publisher version: | http://dx.doi.org/10.1038/ejhg.2014.261 |
| Language: | English |
| Additional information: | © 2014 Macmillan Publishers Limited. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder in order to reproduce the material. |
| Keywords: | SLC1A2, EAAT2, GLT1, Bipolar disorder, Schizophrenia, Rare variants |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Division of Psychiatry UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Ophthalmology |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/1455550 |
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