Gene variants associated with schizophrenia in a Norwegian genome-wide study are replicated in a large European cohort
Abstract We have performed a genome-wide association study (GWAS) of schizophrenia in a Norwegian discovery sample of 201 cases and 305 controls (TOP study) with a focused replication analysis in a larger European sample of 2663 cases and 13,780 control subjects (SGENE-plus study). Firstly, the disc...
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| creator | Athanasiu, Lavinia Mattingsdal, Morten Kähler, Anna K Brown, Andrew Gustafsson, Omar Agartz, Ingrid Giegling, Ina Muglia, Pierandrea Cichon, Sven Rietschel, Marcella Pietiläinen, Olli P.H Peltonen, Leena Bramon, Elvira Collier, David Clair, David St Sigurdsson, Engilbert Petursson, Hannes Rujescu, Dan Melle, Ingrid Steen, Vidar M Djurovic, Srdjan Andreassen, Ole A |
| description | Abstract We have performed a genome-wide association study (GWAS) of schizophrenia in a Norwegian discovery sample of 201 cases and 305 controls (TOP study) with a focused replication analysis in a larger European sample of 2663 cases and 13,780 control subjects (SGENE-plus study). Firstly, the discovery sample was genotyped with Affymetrix Genome-Wide Human SNP Array 6.0 and 572,888 markers were tested for schizophrenia association. No SNPs in the discovery sample attained genome-wide significance ( P < 8.7 × 10−8 ). Secondly, based on the GWAS data, we selected 1000 markers with the lowest P values in the discovery TOP sample, and tested these (or HapMap-based surrogates) for association in the replication sample. Sixteen loci were associated with schizophrenia (nominal P value < 0.05 and concurring OR) in the replication sample. As a next step, we performed a combined analysis of the findings from these two studies, and the strongest evidence for association with schizophrenia was provided for markers rs7045881 on 9p21, rs433598 on 16p12 and rs10761482 on 10q21. The markers are located in PLAA , ACSM 1 and ANK 3, respectively. PLAA has not previously been described as a susceptibility gene, but 9p21 is implied as a schizophrenia linkage region. ACSM 1 has been identified as a susceptibility gene in a previous schizophrenia GWAS study. The association of ANK 3 with schizophrenia is intriguing in light of recent associations of ANK 3 with bipolar disorder, thereby supporting the hypothesis of an overlap in genetic susceptibility between these psychopathological entities. |
| doi_str_mv | 10.1016/j.jpsychires.2010.02.002 |
| format | Article |
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Firstly, the discovery sample was genotyped with Affymetrix Genome-Wide Human SNP Array 6.0 and 572,888 markers were tested for schizophrenia association. No SNPs in the discovery sample attained genome-wide significance ( P < 8.7 × 10−8 ). Secondly, based on the GWAS data, we selected 1000 markers with the lowest P values in the discovery TOP sample, and tested these (or HapMap-based surrogates) for association in the replication sample. Sixteen loci were associated with schizophrenia (nominal P value < 0.05 and concurring OR) in the replication sample. As a next step, we performed a combined analysis of the findings from these two studies, and the strongest evidence for association with schizophrenia was provided for markers rs7045881 on 9p21, rs433598 on 16p12 and rs10761482 on 10q21. The markers are located in PLAA , ACSM 1 and ANK 3, respectively. PLAA has not previously been described as a susceptibility gene, but 9p21 is implied as a schizophrenia linkage region. ACSM 1 has been identified as a susceptibility gene in a previous schizophrenia GWAS study. The association of ANK 3 with schizophrenia is intriguing in light of recent associations of ANK 3 with bipolar disorder, thereby supporting the hypothesis of an overlap in genetic susceptibility between these psychopathological entities.</description><identifier>ISSN: 0022-3956</identifier><identifier>ISSN: 1879-1379</identifier><identifier>EISSN: 1879-1379</identifier><identifier>DOI: 10.1016/j.jpsychires.2010.02.002</identifier><identifier>PMID: 20185149</identifier><identifier>CODEN: JPYRA3</identifier><language>eng</language><publisher>Kidlington: Elsevier Ltd</publisher><subject>ACSM1 ; Adult and adolescent clinical studies ; ANK3 ; Ankyrins - genetics ; Biological and medical sciences ; Bipolar disorder ; Coenzyme A Ligases - genetics ; Cohort Studies ; Data processing ; Discovery ; Europe - epidemiology ; Female ; Genes ; Genome-Wide Association Study ; Humans ; Linkage Disequilibrium ; Male ; Medical sciences ; Mental disorders ; Norway ; Norway - epidemiology ; PLAA ; Polymorphism, Single Nucleotide - genetics ; Proteins - genetics ; Psychiatric genetics ; Psychiatry ; Psychology. Psychoanalysis. Psychiatry ; Psychopathology. Psychiatry ; Psychoses ; Reference Values ; Replication ; Retrospective Studies ; Schizophrenia ; Schizophrenia - epidemiology ; Schizophrenia - genetics ; Single-nucleotide polymorphism ; Surrogates ; Susceptibility ; White People</subject><ispartof>Journal of psychiatric research, 2010-09, Vol.44 (12), p.748-753</ispartof><rights>Elsevier Ltd</rights><rights>2010 Elsevier Ltd</rights><rights>2015 INIST-CNRS</rights><rights>Copyright (c) 2010 Elsevier Ltd. All rights reserved.</rights><rights>Copyright (c) 2010 Elsevier Ltd. All rights reserved.</rights><rights>2010 Elsevier Ltd. All rights reserved. 2010</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c628t-6de45a7d122a6691e9c09bf96a226527ced30a64848e497ca86616863629ea923</citedby><cites>FETCH-LOGICAL-c628t-6de45a7d122a6691e9c09bf96a226527ced30a64848e497ca86616863629ea923</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.jpsychires.2010.02.002$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,777,781,882,3537,27905,27906,30981,45976</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=23157625$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20185149$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Athanasiu, Lavinia</creatorcontrib><creatorcontrib>Mattingsdal, Morten</creatorcontrib><creatorcontrib>Kähler, Anna K</creatorcontrib><creatorcontrib>Brown, Andrew</creatorcontrib><creatorcontrib>Gustafsson, Omar</creatorcontrib><creatorcontrib>Agartz, Ingrid</creatorcontrib><creatorcontrib>Giegling, Ina</creatorcontrib><creatorcontrib>Muglia, Pierandrea</creatorcontrib><creatorcontrib>Cichon, Sven</creatorcontrib><creatorcontrib>Rietschel, Marcella</creatorcontrib><creatorcontrib>Pietiläinen, Olli P.H</creatorcontrib><creatorcontrib>Peltonen, Leena</creatorcontrib><creatorcontrib>Bramon, Elvira</creatorcontrib><creatorcontrib>Collier, David</creatorcontrib><creatorcontrib>Clair, David St</creatorcontrib><creatorcontrib>Sigurdsson, Engilbert</creatorcontrib><creatorcontrib>Petursson, Hannes</creatorcontrib><creatorcontrib>Rujescu, Dan</creatorcontrib><creatorcontrib>Melle, Ingrid</creatorcontrib><creatorcontrib>Steen, Vidar M</creatorcontrib><creatorcontrib>Djurovic, Srdjan</creatorcontrib><creatorcontrib>Andreassen, Ole A</creatorcontrib><title>Gene variants associated with schizophrenia in a Norwegian genome-wide study are replicated in a large European cohort</title><title>Journal of psychiatric research</title><addtitle>J Psychiatr Res</addtitle><description>Abstract We have performed a genome-wide association study (GWAS) of schizophrenia in a Norwegian discovery sample of 201 cases and 305 controls (TOP study) with a focused replication analysis in a larger European sample of 2663 cases and 13,780 control subjects (SGENE-plus study). Firstly, the discovery sample was genotyped with Affymetrix Genome-Wide Human SNP Array 6.0 and 572,888 markers were tested for schizophrenia association. No SNPs in the discovery sample attained genome-wide significance ( P < 8.7 × 10−8 ). Secondly, based on the GWAS data, we selected 1000 markers with the lowest P values in the discovery TOP sample, and tested these (or HapMap-based surrogates) for association in the replication sample. Sixteen loci were associated with schizophrenia (nominal P value < 0.05 and concurring OR) in the replication sample. As a next step, we performed a combined analysis of the findings from these two studies, and the strongest evidence for association with schizophrenia was provided for markers rs7045881 on 9p21, rs433598 on 16p12 and rs10761482 on 10q21. The markers are located in PLAA , ACSM 1 and ANK 3, respectively. PLAA has not previously been described as a susceptibility gene, but 9p21 is implied as a schizophrenia linkage region. ACSM 1 has been identified as a susceptibility gene in a previous schizophrenia GWAS study. The association of ANK 3 with schizophrenia is intriguing in light of recent associations of ANK 3 with bipolar disorder, thereby supporting the hypothesis of an overlap in genetic susceptibility between these psychopathological entities.</description><subject>ACSM1</subject><subject>Adult and adolescent clinical studies</subject><subject>ANK3</subject><subject>Ankyrins - genetics</subject><subject>Biological and medical sciences</subject><subject>Bipolar disorder</subject><subject>Coenzyme A Ligases - genetics</subject><subject>Cohort Studies</subject><subject>Data processing</subject><subject>Discovery</subject><subject>Europe - epidemiology</subject><subject>Female</subject><subject>Genes</subject><subject>Genome-Wide Association Study</subject><subject>Humans</subject><subject>Linkage Disequilibrium</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Mental disorders</subject><subject>Norway</subject><subject>Norway - epidemiology</subject><subject>PLAA</subject><subject>Polymorphism, Single Nucleotide - genetics</subject><subject>Proteins - genetics</subject><subject>Psychiatric genetics</subject><subject>Psychiatry</subject><subject>Psychology. Psychoanalysis. Psychiatry</subject><subject>Psychopathology. Psychiatry</subject><subject>Psychoses</subject><subject>Reference Values</subject><subject>Replication</subject><subject>Retrospective Studies</subject><subject>Schizophrenia</subject><subject>Schizophrenia - epidemiology</subject><subject>Schizophrenia - genetics</subject><subject>Single-nucleotide polymorphism</subject><subject>Surrogates</subject><subject>Susceptibility</subject><subject>White People</subject><issn>0022-3956</issn><issn>1879-1379</issn><issn>1879-1379</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>7QJ</sourceid><recordid>eNqNkk9vEzEQxVcIREPhKyBfEFw22N5d_7lUolUpSBUcgLM19U4Sh4292LuJwqfH24QWOAAnS-PfezP2vKIgjM4ZZeL1er7u096uXMQ05zSXKZ9Tyh8UM6akLlkl9cNiliu8rHQjToonKa0ppZKz-nFxkiWqYbWeFdsr9Ei2EB34IRFIKVgHA7Zk54YVSbnH99CvInoHxHkC5EOIO1xmnCzRhw2WO9ciScPY7glEJBH7ztlbi1u-g7hEcjnG0GMW2bAKcXhaPFpAl_DZ8Twtvry9_Hzxrrz-ePX-4s11aQVXQylarBuQLeMchNAMtaX6ZqEFcC4aLi22FQVRq1phraUFJQQTSlSCawTNq9Pi7ODbjzcbbC36IUJn-ug2EPcmgDO_33i3MsuwNRXntdZ1Nnh5NIjh24hpMBuXLHYdeAxjMlJyLhWl6t9krbSQTMhMvvoryRhveFU1ajJVB9TGkFLExd3ojJopCmZt7qNgpigYyk1efJY-__Xpd8Kfu8_AiyMAyUK3iOCtS_dcxRopeJO58wOHeVFbh9Ek69Dnv8897WDa4P5nmrM_TGznfM5J9xX3mNZhjD4HwTCTssB8mqI7JZfl0NJKsOoHB6PtjQ</recordid><startdate>20100901</startdate><enddate>20100901</enddate><creator>Athanasiu, Lavinia</creator><creator>Mattingsdal, Morten</creator><creator>Kähler, Anna K</creator><creator>Brown, Andrew</creator><creator>Gustafsson, Omar</creator><creator>Agartz, Ingrid</creator><creator>Giegling, Ina</creator><creator>Muglia, Pierandrea</creator><creator>Cichon, Sven</creator><creator>Rietschel, Marcella</creator><creator>Pietiläinen, Olli P.H</creator><creator>Peltonen, Leena</creator><creator>Bramon, Elvira</creator><creator>Collier, David</creator><creator>Clair, David St</creator><creator>Sigurdsson, Engilbert</creator><creator>Petursson, Hannes</creator><creator>Rujescu, Dan</creator><creator>Melle, Ingrid</creator><creator>Steen, Vidar M</creator><creator>Djurovic, Srdjan</creator><creator>Andreassen, Ole A</creator><general>Elsevier Ltd</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>7TK</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>7QJ</scope><scope>5PM</scope></search><sort><creationdate>20100901</creationdate><title>Gene variants associated with schizophrenia in a Norwegian genome-wide study are replicated in a large European cohort</title><author>Athanasiu, Lavinia ; Mattingsdal, Morten ; Kähler, Anna K ; Brown, Andrew ; Gustafsson, Omar ; Agartz, Ingrid ; Giegling, Ina ; Muglia, Pierandrea ; Cichon, Sven ; Rietschel, Marcella ; Pietiläinen, Olli P.H ; Peltonen, Leena ; Bramon, Elvira ; Collier, David ; Clair, David St ; Sigurdsson, Engilbert ; Petursson, Hannes ; Rujescu, Dan ; Melle, Ingrid ; Steen, Vidar M ; Djurovic, Srdjan ; Andreassen, Ole A</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c628t-6de45a7d122a6691e9c09bf96a226527ced30a64848e497ca86616863629ea923</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>ACSM1</topic><topic>Adult and adolescent clinical studies</topic><topic>ANK3</topic><topic>Ankyrins - genetics</topic><topic>Biological and medical sciences</topic><topic>Bipolar disorder</topic><topic>Coenzyme A Ligases - genetics</topic><topic>Cohort Studies</topic><topic>Data processing</topic><topic>Discovery</topic><topic>Europe - epidemiology</topic><topic>Female</topic><topic>Genes</topic><topic>Genome-Wide Association Study</topic><topic>Humans</topic><topic>Linkage Disequilibrium</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Mental disorders</topic><topic>Norway</topic><topic>Norway - epidemiology</topic><topic>PLAA</topic><topic>Polymorphism, Single Nucleotide - genetics</topic><topic>Proteins - genetics</topic><topic>Psychiatric genetics</topic><topic>Psychiatry</topic><topic>Psychology. 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Psychiatry</topic><topic>Psychoses</topic><topic>Reference Values</topic><topic>Replication</topic><topic>Retrospective Studies</topic><topic>Schizophrenia</topic><topic>Schizophrenia - epidemiology</topic><topic>Schizophrenia - genetics</topic><topic>Single-nucleotide polymorphism</topic><topic>Surrogates</topic><topic>Susceptibility</topic><topic>White People</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Athanasiu, Lavinia</creatorcontrib><creatorcontrib>Mattingsdal, Morten</creatorcontrib><creatorcontrib>Kähler, Anna K</creatorcontrib><creatorcontrib>Brown, Andrew</creatorcontrib><creatorcontrib>Gustafsson, Omar</creatorcontrib><creatorcontrib>Agartz, Ingrid</creatorcontrib><creatorcontrib>Giegling, Ina</creatorcontrib><creatorcontrib>Muglia, Pierandrea</creatorcontrib><creatorcontrib>Cichon, Sven</creatorcontrib><creatorcontrib>Rietschel, Marcella</creatorcontrib><creatorcontrib>Pietiläinen, Olli P.H</creatorcontrib><creatorcontrib>Peltonen, Leena</creatorcontrib><creatorcontrib>Bramon, Elvira</creatorcontrib><creatorcontrib>Collier, David</creatorcontrib><creatorcontrib>Clair, David St</creatorcontrib><creatorcontrib>Sigurdsson, Engilbert</creatorcontrib><creatorcontrib>Petursson, Hannes</creatorcontrib><creatorcontrib>Rujescu, Dan</creatorcontrib><creatorcontrib>Melle, Ingrid</creatorcontrib><creatorcontrib>Steen, Vidar M</creatorcontrib><creatorcontrib>Djurovic, Srdjan</creatorcontrib><creatorcontrib>Andreassen, Ole 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>Neurosciences Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>Applied Social Sciences Index & Abstracts (ASSIA)</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Journal of psychiatric research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Athanasiu, Lavinia</au><au>Mattingsdal, Morten</au><au>Kähler, Anna K</au><au>Brown, Andrew</au><au>Gustafsson, Omar</au><au>Agartz, Ingrid</au><au>Giegling, Ina</au><au>Muglia, Pierandrea</au><au>Cichon, Sven</au><au>Rietschel, Marcella</au><au>Pietiläinen, Olli P.H</au><au>Peltonen, Leena</au><au>Bramon, Elvira</au><au>Collier, David</au><au>Clair, David St</au><au>Sigurdsson, Engilbert</au><au>Petursson, Hannes</au><au>Rujescu, Dan</au><au>Melle, Ingrid</au><au>Steen, Vidar M</au><au>Djurovic, Srdjan</au><au>Andreassen, Ole A</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Gene variants associated with schizophrenia in a Norwegian genome-wide study are replicated in a large European cohort</atitle><jtitle>Journal of psychiatric research</jtitle><addtitle>J Psychiatr Res</addtitle><date>2010-09-01</date><risdate>2010</risdate><volume>44</volume><issue>12</issue><spage>748</spage><epage>753</epage><pages>748-753</pages><issn>0022-3956</issn><issn>1879-1379</issn><eissn>1879-1379</eissn><coden>JPYRA3</coden><abstract>Abstract We have performed a genome-wide association study (GWAS) of schizophrenia in a Norwegian discovery sample of 201 cases and 305 controls (TOP study) with a focused replication analysis in a larger European sample of 2663 cases and 13,780 control subjects (SGENE-plus study). Firstly, the discovery sample was genotyped with Affymetrix Genome-Wide Human SNP Array 6.0 and 572,888 markers were tested for schizophrenia association. No SNPs in the discovery sample attained genome-wide significance ( P < 8.7 × 10−8 ). Secondly, based on the GWAS data, we selected 1000 markers with the lowest P values in the discovery TOP sample, and tested these (or HapMap-based surrogates) for association in the replication sample. Sixteen loci were associated with schizophrenia (nominal P value < 0.05 and concurring OR) in the replication sample. As a next step, we performed a combined analysis of the findings from these two studies, and the strongest evidence for association with schizophrenia was provided for markers rs7045881 on 9p21, rs433598 on 16p12 and rs10761482 on 10q21. The markers are located in PLAA , ACSM 1 and ANK 3, respectively. PLAA has not previously been described as a susceptibility gene, but 9p21 is implied as a schizophrenia linkage region. ACSM 1 has been identified as a susceptibility gene in a previous schizophrenia GWAS study. The association of ANK 3 with schizophrenia is intriguing in light of recent associations of ANK 3 with bipolar disorder, thereby supporting the hypothesis of an overlap in genetic susceptibility between these psychopathological entities.</abstract><cop>Kidlington</cop><pub>Elsevier Ltd</pub><pmid>20185149</pmid><doi>10.1016/j.jpsychires.2010.02.002</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | ACSM1 Adult and adolescent clinical studies ANK3 Ankyrins - genetics Biological and medical sciences Bipolar disorder Coenzyme A Ligases - genetics Cohort Studies Data processing Discovery Europe - epidemiology Female Genes Genome-Wide Association Study Humans Linkage Disequilibrium Male Medical sciences Mental disorders Norway Norway - epidemiology PLAA Polymorphism, Single Nucleotide - genetics Proteins - genetics Psychiatric genetics Psychiatry Psychology. Psychoanalysis. Psychiatry Psychopathology. Psychiatry Psychoses Reference Values Replication Retrospective Studies Schizophrenia Schizophrenia - epidemiology Schizophrenia - genetics Single-nucleotide polymorphism Surrogates Susceptibility White People |
| title | Gene variants associated with schizophrenia in a Norwegian genome-wide study are replicated in a large European cohort |
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