A possible association between schizophrenia and GRIK3 polymorphisms in a multicenter sample of Scandinavian origin (SCOPE)
Abstract There is considerable evidence of altered glutamatergic signalling in schizophrenia and a polymorphic variant of the GRIK3 glutamate receptor gene on 1p34-33 has previously been associated to this psychotic disorder. We therefore conducted a systematic association study with 30 HapMap-selec...
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| creator | Djurovic, S Kähler, A.K Kulle, B Jönsson, E.G Agartz, I Le Hellard, S Hall, H Jakobsen, K.D Hansen, T Melle, I Werge, T Steen, V.M Andreassen, O.A |
| description | Abstract There is considerable evidence of altered glutamatergic signalling in schizophrenia and a polymorphic variant of the GRIK3 glutamate receptor gene on 1p34-33 has previously been associated to this psychotic disorder. We therefore conducted a systematic association study with 30 HapMap-selected tagging SNPs across GRIK3 in three independent samples of Scandinavian origin from the Scandinavian Collaboration of Psychiatric Etiology (SCOPE), including a total of 839 cases with schizophrenia spectrum and 1473 healthy controls. Four markers (rs6671364, rs17461259, rs472188, and rs535620) attained nominally significant P -values in both the genotypic (0.002, 0.02, 0.03, and 0.05, respectively) and allelic (0.001, 0.006, 0.03, and 0.02, respectively) association tests for the combined sample, and 2 additional markers (rs481047and rs1160751) displayed significance for the genotype ( P -values: 0.03 and 0.04). Several haplotypes, that all included at least one of the four SNPs implicated by the single marker analysis, remained significant after adjustment for multiple testing using permutations with 10,000 shuffles. In addition we observed an association for two of the four significant GRIK3 markers (rs472188 and rs535620) to scores for negative symptoms on the PANSS scale. The present results, although not robust, support the importance of more extensive investigations of GRIK3 , given its potential role in mediating risk for schizophrenia. |
| doi_str_mv | 10.1016/j.schres.2008.10.010 |
| format | Article |
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We therefore conducted a systematic association study with 30 HapMap-selected tagging SNPs across GRIK3 in three independent samples of Scandinavian origin from the Scandinavian Collaboration of Psychiatric Etiology (SCOPE), including a total of 839 cases with schizophrenia spectrum and 1473 healthy controls. Four markers (rs6671364, rs17461259, rs472188, and rs535620) attained nominally significant P -values in both the genotypic (0.002, 0.02, 0.03, and 0.05, respectively) and allelic (0.001, 0.006, 0.03, and 0.02, respectively) association tests for the combined sample, and 2 additional markers (rs481047and rs1160751) displayed significance for the genotype ( P -values: 0.03 and 0.04). Several haplotypes, that all included at least one of the four SNPs implicated by the single marker analysis, remained significant after adjustment for multiple testing using permutations with 10,000 shuffles. In addition we observed an association for two of the four significant GRIK3 markers (rs472188 and rs535620) to scores for negative symptoms on the PANSS scale. The present results, although not robust, support the importance of more extensive investigations of GRIK3 , given its potential role in mediating risk for schizophrenia.</description><identifier>ISSN: 0920-9964</identifier><identifier>EISSN: 1573-2509</identifier><identifier>DOI: 10.1016/j.schres.2008.10.010</identifier><identifier>PMID: 19022628</identifier><language>eng</language><publisher>Amsterdam: Elsevier B.V</publisher><subject>Adult ; Adult and adolescent clinical studies ; Alleles ; Biological and medical sciences ; Candidate gene ; Chromosomes, Human, Pair 1 - genetics ; Female ; Genetic association ; Genetic Markers - genetics ; Genotype ; GluK3 Kainate Receptor ; Glutamate ; GRIK3 ; Haplotypes ; Humans ; Linkage Disequilibrium - genetics ; Male ; Medical sciences ; Middle Aged ; Polymorphism, Genetic - genetics ; Polymorphism, Single Nucleotide - genetics ; Psychiatric Status Rating Scales ; Psychiatry ; Psychology. Psychoanalysis. Psychiatry ; Psychopathology. Psychiatry ; Psychoses ; Psychotic Disorders - diagnosis ; Psychotic Disorders - genetics ; Psychotic Disorders - psychology ; Receptors, Kainic Acid - genetics ; Scandinavian and Nordic Countries ; Schizophrenia ; Schizophrenia - diagnosis ; Schizophrenia - genetics ; Schizophrenic Psychology</subject><ispartof>Schizophrenia research, 2009-02, Vol.107 (2), p.242-248</ispartof><rights>Elsevier B.V.</rights><rights>2008 Elsevier B.V.</rights><rights>2009 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c483t-cfb406cdd313dfb381773bb3d382315536b775d9910e97d21473be03d29ad54b3</citedby><cites>FETCH-LOGICAL-c483t-cfb406cdd313dfb381773bb3d382315536b775d9910e97d21473be03d29ad54b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0920996408004684$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,776,780,881,3536,27903,27904,65309</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=21145764$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19022628$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttp://kipublications.ki.se/Default.aspx?queryparsed=id:118344023$$DView record from Swedish Publication Index$$Hfree_for_read</backlink></links><search><creatorcontrib>Djurovic, S</creatorcontrib><creatorcontrib>Kähler, A.K</creatorcontrib><creatorcontrib>Kulle, B</creatorcontrib><creatorcontrib>Jönsson, E.G</creatorcontrib><creatorcontrib>Agartz, I</creatorcontrib><creatorcontrib>Le Hellard, S</creatorcontrib><creatorcontrib>Hall, H</creatorcontrib><creatorcontrib>Jakobsen, K.D</creatorcontrib><creatorcontrib>Hansen, T</creatorcontrib><creatorcontrib>Melle, I</creatorcontrib><creatorcontrib>Werge, T</creatorcontrib><creatorcontrib>Steen, V.M</creatorcontrib><creatorcontrib>Andreassen, O.A</creatorcontrib><title>A possible association between schizophrenia and GRIK3 polymorphisms in a multicenter sample of Scandinavian origin (SCOPE)</title><title>Schizophrenia research</title><addtitle>Schizophr Res</addtitle><description>Abstract There is considerable evidence of altered glutamatergic signalling in schizophrenia and a polymorphic variant of the GRIK3 glutamate receptor gene on 1p34-33 has previously been associated to this psychotic disorder. We therefore conducted a systematic association study with 30 HapMap-selected tagging SNPs across GRIK3 in three independent samples of Scandinavian origin from the Scandinavian Collaboration of Psychiatric Etiology (SCOPE), including a total of 839 cases with schizophrenia spectrum and 1473 healthy controls. Four markers (rs6671364, rs17461259, rs472188, and rs535620) attained nominally significant P -values in both the genotypic (0.002, 0.02, 0.03, and 0.05, respectively) and allelic (0.001, 0.006, 0.03, and 0.02, respectively) association tests for the combined sample, and 2 additional markers (rs481047and rs1160751) displayed significance for the genotype ( P -values: 0.03 and 0.04). Several haplotypes, that all included at least one of the four SNPs implicated by the single marker analysis, remained significant after adjustment for multiple testing using permutations with 10,000 shuffles. In addition we observed an association for two of the four significant GRIK3 markers (rs472188 and rs535620) to scores for negative symptoms on the PANSS scale. The present results, although not robust, support the importance of more extensive investigations of GRIK3 , given its potential role in mediating risk for schizophrenia.</description><subject>Adult</subject><subject>Adult and adolescent clinical studies</subject><subject>Alleles</subject><subject>Biological and medical sciences</subject><subject>Candidate gene</subject><subject>Chromosomes, Human, Pair 1 - genetics</subject><subject>Female</subject><subject>Genetic association</subject><subject>Genetic Markers - genetics</subject><subject>Genotype</subject><subject>GluK3 Kainate Receptor</subject><subject>Glutamate</subject><subject>GRIK3</subject><subject>Haplotypes</subject><subject>Humans</subject><subject>Linkage Disequilibrium - genetics</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Polymorphism, Genetic - genetics</subject><subject>Polymorphism, Single Nucleotide - genetics</subject><subject>Psychiatric Status Rating Scales</subject><subject>Psychiatry</subject><subject>Psychology. Psychoanalysis. Psychiatry</subject><subject>Psychopathology. Psychiatry</subject><subject>Psychoses</subject><subject>Psychotic Disorders - diagnosis</subject><subject>Psychotic Disorders - genetics</subject><subject>Psychotic Disorders - psychology</subject><subject>Receptors, Kainic Acid - genetics</subject><subject>Scandinavian and Nordic Countries</subject><subject>Schizophrenia</subject><subject>Schizophrenia - diagnosis</subject><subject>Schizophrenia - genetics</subject><subject>Schizophrenic Psychology</subject><issn>0920-9964</issn><issn>1573-2509</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkkFv1DAQhSMEokvhHyDkCwgOWcZ24iQXpGpVSkWlIhbOlmNPqLeJHeyk1cKfx9GuisSFk63xN-9Z8ybLXlJYU6Di_W4d9U3AuGYAdSqtgcKjbEXLiueshOZxtoKGQd40ojjJnsW4AwBaQvU0O6ENMCZYvcp-n5HRx2jbHomK0WurJusdaXG6R3QkedhffkxGziqinCEXXy8_89TU7wcfxhsbh0isI4oMcz9ZjW7CQKIaxqToO7LVqck6dWeVIz7YH4l9u91cfzl_9zx70qk-4ovjeZp9_3j-bfMpv7q-uNycXeW6qPmU664tQGhjOOWma3lNq4q3LTe8ZpyWJRdtVZWmaShgUxlGi_SMwA1rlCmLlp9m-UE33uM4t3IMdlBhL72y8li6TTeUpaBU1Il_c-DH4H_OGCc52Kix75VDP0cpRF2IqhYJLA6gDmmGAbsHaQpyCUnu5CEkuYS0VFNIqe3VUX9uBzR_m46pJOD1EVBRq74LymkbHzhGaVFWokjchwOHaXp3FkNys-g0GhtQT9J4-7-f_Cuge-ts8rzFPcadn4NLyUgqI5Mgt8tCLfsENUCRpsD_AL4yx7Q</recordid><startdate>20090201</startdate><enddate>20090201</enddate><creator>Djurovic, S</creator><creator>Kähler, A.K</creator><creator>Kulle, B</creator><creator>Jönsson, E.G</creator><creator>Agartz, I</creator><creator>Le Hellard, S</creator><creator>Hall, H</creator><creator>Jakobsen, K.D</creator><creator>Hansen, T</creator><creator>Melle, I</creator><creator>Werge, T</creator><creator>Steen, V.M</creator><creator>Andreassen, O.A</creator><general>Elsevier B.V</general><general>Elsevier</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>ADTPV</scope><scope>AOWAS</scope></search><sort><creationdate>20090201</creationdate><title>A possible association between schizophrenia and GRIK3 polymorphisms in a multicenter sample of Scandinavian origin (SCOPE)</title><author>Djurovic, S ; Kähler, A.K ; Kulle, B ; Jönsson, E.G ; Agartz, I ; Le Hellard, S ; Hall, H ; Jakobsen, K.D ; Hansen, T ; Melle, I ; Werge, T ; Steen, V.M ; Andreassen, O.A</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c483t-cfb406cdd313dfb381773bb3d382315536b775d9910e97d21473be03d29ad54b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Adult</topic><topic>Adult and adolescent clinical studies</topic><topic>Alleles</topic><topic>Biological and medical sciences</topic><topic>Candidate gene</topic><topic>Chromosomes, Human, Pair 1 - genetics</topic><topic>Female</topic><topic>Genetic association</topic><topic>Genetic Markers - genetics</topic><topic>Genotype</topic><topic>GluK3 Kainate Receptor</topic><topic>Glutamate</topic><topic>GRIK3</topic><topic>Haplotypes</topic><topic>Humans</topic><topic>Linkage Disequilibrium - genetics</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Polymorphism, Genetic - genetics</topic><topic>Polymorphism, Single Nucleotide - genetics</topic><topic>Psychiatric Status Rating Scales</topic><topic>Psychiatry</topic><topic>Psychology. Psychoanalysis. Psychiatry</topic><topic>Psychopathology. Psychiatry</topic><topic>Psychoses</topic><topic>Psychotic Disorders - diagnosis</topic><topic>Psychotic Disorders - genetics</topic><topic>Psychotic Disorders - psychology</topic><topic>Receptors, Kainic Acid - genetics</topic><topic>Scandinavian and Nordic Countries</topic><topic>Schizophrenia</topic><topic>Schizophrenia - diagnosis</topic><topic>Schizophrenia - genetics</topic><topic>Schizophrenic Psychology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Djurovic, S</creatorcontrib><creatorcontrib>Kähler, A.K</creatorcontrib><creatorcontrib>Kulle, B</creatorcontrib><creatorcontrib>Jönsson, E.G</creatorcontrib><creatorcontrib>Agartz, I</creatorcontrib><creatorcontrib>Le Hellard, S</creatorcontrib><creatorcontrib>Hall, H</creatorcontrib><creatorcontrib>Jakobsen, K.D</creatorcontrib><creatorcontrib>Hansen, T</creatorcontrib><creatorcontrib>Melle, I</creatorcontrib><creatorcontrib>Werge, T</creatorcontrib><creatorcontrib>Steen, V.M</creatorcontrib><creatorcontrib>Andreassen, O.A</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>SwePub</collection><collection>SwePub Articles</collection><jtitle>Schizophrenia research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Djurovic, S</au><au>Kähler, A.K</au><au>Kulle, B</au><au>Jönsson, E.G</au><au>Agartz, I</au><au>Le Hellard, S</au><au>Hall, H</au><au>Jakobsen, K.D</au><au>Hansen, T</au><au>Melle, I</au><au>Werge, T</au><au>Steen, V.M</au><au>Andreassen, O.A</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A possible association between schizophrenia and GRIK3 polymorphisms in a multicenter sample of Scandinavian origin (SCOPE)</atitle><jtitle>Schizophrenia research</jtitle><addtitle>Schizophr Res</addtitle><date>2009-02-01</date><risdate>2009</risdate><volume>107</volume><issue>2</issue><spage>242</spage><epage>248</epage><pages>242-248</pages><issn>0920-9964</issn><eissn>1573-2509</eissn><abstract>Abstract There is considerable evidence of altered glutamatergic signalling in schizophrenia and a polymorphic variant of the GRIK3 glutamate receptor gene on 1p34-33 has previously been associated to this psychotic disorder. We therefore conducted a systematic association study with 30 HapMap-selected tagging SNPs across GRIK3 in three independent samples of Scandinavian origin from the Scandinavian Collaboration of Psychiatric Etiology (SCOPE), including a total of 839 cases with schizophrenia spectrum and 1473 healthy controls. Four markers (rs6671364, rs17461259, rs472188, and rs535620) attained nominally significant P -values in both the genotypic (0.002, 0.02, 0.03, and 0.05, respectively) and allelic (0.001, 0.006, 0.03, and 0.02, respectively) association tests for the combined sample, and 2 additional markers (rs481047and rs1160751) displayed significance for the genotype ( P -values: 0.03 and 0.04). Several haplotypes, that all included at least one of the four SNPs implicated by the single marker analysis, remained significant after adjustment for multiple testing using permutations with 10,000 shuffles. In addition we observed an association for two of the four significant GRIK3 markers (rs472188 and rs535620) to scores for negative symptoms on the PANSS scale. The present results, although not robust, support the importance of more extensive investigations of GRIK3 , given its potential role in mediating risk for schizophrenia.</abstract><cop>Amsterdam</cop><pub>Elsevier B.V</pub><pmid>19022628</pmid><doi>10.1016/j.schres.2008.10.010</doi><tpages>7</tpages></addata></record> |
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| subjects | Adult Adult and adolescent clinical studies Alleles Biological and medical sciences Candidate gene Chromosomes, Human, Pair 1 - genetics Female Genetic association Genetic Markers - genetics Genotype GluK3 Kainate Receptor Glutamate GRIK3 Haplotypes Humans Linkage Disequilibrium - genetics Male Medical sciences Middle Aged Polymorphism, Genetic - genetics Polymorphism, Single Nucleotide - genetics Psychiatric Status Rating Scales Psychiatry Psychology. Psychoanalysis. Psychiatry Psychopathology. Psychiatry Psychoses Psychotic Disorders - diagnosis Psychotic Disorders - genetics Psychotic Disorders - psychology Receptors, Kainic Acid - genetics Scandinavian and Nordic Countries Schizophrenia Schizophrenia - diagnosis Schizophrenia - genetics Schizophrenic Psychology |
| title | A possible association between schizophrenia and GRIK3 polymorphisms in a multicenter sample of Scandinavian origin (SCOPE) |
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