Impact of Schizophrenia Candidate Genes on Schizotypy and Cognitive Endophenotypes at the Population Level
Background Aspects of cognitive function and schizotypy have been proposed as potential endophenotypes for schizophrenia. It is unknown whether the expression of these endophenotypes at the population level is modulated by the genetic variability of candidate susceptibility genes for schizophrenia....
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description | Background Aspects of cognitive function and schizotypy have been proposed as potential endophenotypes for schizophrenia. It is unknown whether the expression of these endophenotypes at the population level is modulated by the genetic variability of candidate susceptibility genes for schizophrenia. Methods We examined the potential impact of 18 single nucleotide polymorphisms (SNPs) within the DTNBP1 , NRG1 , DAOA/G32 , and DAAO genes, on cognition and self-rated schizotypy, in a representative population of 2243 young male military conscripts. Single SNP and haplotype associations were evaluated. Results The DTNBP1 SNPs rs2619522 and rs760761 exhibited several single marker associations, the minor alleles being associated with lower attention capacity but also a decrease in positive and paranoid schizotypy scores. The DTNBP1 haplotype load had borderline associations with nonverbal IQ, paranoid schizotypy, and sustained attention. For individual NRG1 polymorphisms, isolated but weak signals of association were noted with sustained attention and working memory but not schizotypy. The risk allele of functional SNP8NRG243177 was associated with reduced spatial working memory capacity. An isolated effect of DAAO haplotype variability was noted on negative and disorganization schizotypy. No convincing association of DAOA/G32 variability was detected. Conclusions The DTNBP1 and, less so, NRG1 and DAAO variants might exert gene-specific modulating effects on schizophrenia endophenotypes at the population level. |
doi_str_mv | 10.1016/j.biopsych.2006.11.015 |
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It is unknown whether the expression of these endophenotypes at the population level is modulated by the genetic variability of candidate susceptibility genes for schizophrenia. Methods We examined the potential impact of 18 single nucleotide polymorphisms (SNPs) within the DTNBP1 , NRG1 , DAOA/G32 , and DAAO genes, on cognition and self-rated schizotypy, in a representative population of 2243 young male military conscripts. Single SNP and haplotype associations were evaluated. Results The DTNBP1 SNPs rs2619522 and rs760761 exhibited several single marker associations, the minor alleles being associated with lower attention capacity but also a decrease in positive and paranoid schizotypy scores. The DTNBP1 haplotype load had borderline associations with nonverbal IQ, paranoid schizotypy, and sustained attention. For individual NRG1 polymorphisms, isolated but weak signals of association were noted with sustained attention and working memory but not schizotypy. The risk allele of functional SNP8NRG243177 was associated with reduced spatial working memory capacity. An isolated effect of DAAO haplotype variability was noted on negative and disorganization schizotypy. No convincing association of DAOA/G32 variability was detected. Conclusions The DTNBP1 and, less so, NRG1 and DAAO variants might exert gene-specific modulating effects on schizophrenia endophenotypes at the population level.</description><identifier>ISSN: 0006-3223</identifier><identifier>EISSN: 1873-2402</identifier><identifier>DOI: 10.1016/j.biopsych.2006.11.015</identifier><identifier>PMID: 17336946</identifier><identifier>CODEN: BIPCBF</identifier><language>eng</language><publisher>New York, NY: Elsevier Inc</publisher><subject>Adolescent ; Adult ; Adult and adolescent clinical studies ; Alleles ; Biological and medical sciences ; Carrier Proteins - genetics ; Carrier Proteins - physiology ; Cognition ; Cognition - physiology ; DAAO ; DAOA/G32 ; DNA - genetics ; DTNBP1 ; Dysbindin ; Dystrophin-Associated Proteins ; endophenotype ; Genotype ; Haplotypes ; Humans ; Intelligence Tests ; Linkage Disequilibrium - genetics ; Male ; Medical sciences ; Neuregulin-1 - genetics ; Neuregulin-1 - physiology ; Neuropsychological Tests ; NRG1 ; Personality disorders ; Personality Tests ; Phenotype ; Polymorphism, Single Nucleotide ; Population ; Psychiatry ; Psychology. Psychoanalysis. Psychiatry ; Psychopathology. Psychiatry ; Psychoses ; Risk ; Schizophrenia ; Schizophrenia - genetics ; Schizophrenic Psychology ; Schizotypal Personality Disorder - genetics ; Schizotypal Personality Disorder - psychology ; schizotypy</subject><ispartof>Biological psychiatry (1969), 2007-10, Vol.62 (7), p.784-792</ispartof><rights>Society of Biological Psychiatry</rights><rights>2007 Society of Biological Psychiatry</rights><rights>2007 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c548t-878201f65d3536028edde64bfc17c209be58b37cfc285a487766a3e39fe118743</citedby><cites>FETCH-LOGICAL-c548t-878201f65d3536028edde64bfc17c209be58b37cfc285a487766a3e39fe118743</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.biopsych.2006.11.015$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>315,781,785,3551,27929,27930,46000</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=19110090$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17336946$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Stefanis, Nicholas C</creatorcontrib><creatorcontrib>Trikalinos, Thomas A</creatorcontrib><creatorcontrib>Avramopoulos, Dimitrios</creatorcontrib><creatorcontrib>Smyrnis, Nikos</creatorcontrib><creatorcontrib>Evdokimidis, Ioannis</creatorcontrib><creatorcontrib>Ntzani, Evangelia E</creatorcontrib><creatorcontrib>Ioannidis, John P</creatorcontrib><creatorcontrib>Stefanis, Costas N</creatorcontrib><title>Impact of Schizophrenia Candidate Genes on Schizotypy and Cognitive Endophenotypes at the Population Level</title><title>Biological psychiatry (1969)</title><addtitle>Biol Psychiatry</addtitle><description>Background Aspects of cognitive function and schizotypy have been proposed as potential endophenotypes for schizophrenia. It is unknown whether the expression of these endophenotypes at the population level is modulated by the genetic variability of candidate susceptibility genes for schizophrenia. Methods We examined the potential impact of 18 single nucleotide polymorphisms (SNPs) within the DTNBP1 , NRG1 , DAOA/G32 , and DAAO genes, on cognition and self-rated schizotypy, in a representative population of 2243 young male military conscripts. Single SNP and haplotype associations were evaluated. Results The DTNBP1 SNPs rs2619522 and rs760761 exhibited several single marker associations, the minor alleles being associated with lower attention capacity but also a decrease in positive and paranoid schizotypy scores. The DTNBP1 haplotype load had borderline associations with nonverbal IQ, paranoid schizotypy, and sustained attention. For individual NRG1 polymorphisms, isolated but weak signals of association were noted with sustained attention and working memory but not schizotypy. The risk allele of functional SNP8NRG243177 was associated with reduced spatial working memory capacity. An isolated effect of DAAO haplotype variability was noted on negative and disorganization schizotypy. No convincing association of DAOA/G32 variability was detected. Conclusions The DTNBP1 and, less so, NRG1 and DAAO variants might exert gene-specific modulating effects on schizophrenia endophenotypes at the population level.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Adult and adolescent clinical studies</subject><subject>Alleles</subject><subject>Biological and medical sciences</subject><subject>Carrier Proteins - genetics</subject><subject>Carrier Proteins - physiology</subject><subject>Cognition</subject><subject>Cognition - physiology</subject><subject>DAAO</subject><subject>DAOA/G32</subject><subject>DNA - genetics</subject><subject>DTNBP1</subject><subject>Dysbindin</subject><subject>Dystrophin-Associated Proteins</subject><subject>endophenotype</subject><subject>Genotype</subject><subject>Haplotypes</subject><subject>Humans</subject><subject>Intelligence Tests</subject><subject>Linkage Disequilibrium - genetics</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Neuregulin-1 - genetics</subject><subject>Neuregulin-1 - physiology</subject><subject>Neuropsychological Tests</subject><subject>NRG1</subject><subject>Personality disorders</subject><subject>Personality Tests</subject><subject>Phenotype</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Population</subject><subject>Psychiatry</subject><subject>Psychology. Psychoanalysis. Psychiatry</subject><subject>Psychopathology. Psychiatry</subject><subject>Psychoses</subject><subject>Risk</subject><subject>Schizophrenia</subject><subject>Schizophrenia - genetics</subject><subject>Schizophrenic Psychology</subject><subject>Schizotypal Personality Disorder - genetics</subject><subject>Schizotypal Personality Disorder - psychology</subject><subject>schizotypy</subject><issn>0006-3223</issn><issn>1873-2402</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkl-L1DAUxYso7rj6FZa86Ftr_rRp-iLKsK4LAwqrzyFNb53UTlKTdKB-elOmsuDLPoVwf-fc5J6bZTcEFwQT_n4oWuOmsOhjQTHmBSEFJtWzbEdEzXJaYvo82-FUyRml7Cp7FcKQrjWl5GV2RWrGeFPyXTbcnyalI3I9etBH88dNRw_WKLRXtjOdioDuwEJAzm5AXKYFpSLau5_WRHMGdGu7pAO71hKqIopHQN_cNI8qmqQ8wBnG19mLXo0B3mzndfbj8-33_Zf88PXufv_pkOuqFDEXtaCY9LzqWMU4pgK6DnjZ9prUmuKmhUq0rNa9pqJSpahrzhUD1vRA0udLdp29u_hO3v2eIUR5MkHDOCoLbg6SC1pXpKqeBCnmAjOxOvILqL0LwUMvJ29Oyi-SYLnGIQf5Lw65xiEJkSmOJLzZOsztCbpH2Tb_BLzdABW0GnuvrDbhkWsIwbjBift44SAN7mzAy6ANWA2d8aCj7Jx5-i0f_rPQo7Emdf0FC4TBzd6mWCSRgUosH9blWXcHc0zSlBv2F5slwVI</recordid><startdate>20071001</startdate><enddate>20071001</enddate><creator>Stefanis, Nicholas C</creator><creator>Trikalinos, Thomas A</creator><creator>Avramopoulos, Dimitrios</creator><creator>Smyrnis, Nikos</creator><creator>Evdokimidis, Ioannis</creator><creator>Ntzani, Evangelia E</creator><creator>Ioannidis, John P</creator><creator>Stefanis, Costas N</creator><general>Elsevier Inc</general><general>Elsevier Science</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></search><sort><creationdate>20071001</creationdate><title>Impact of Schizophrenia Candidate Genes on Schizotypy and Cognitive Endophenotypes at the Population Level</title><author>Stefanis, Nicholas C ; Trikalinos, Thomas A ; Avramopoulos, Dimitrios ; Smyrnis, Nikos ; Evdokimidis, Ioannis ; Ntzani, Evangelia E ; Ioannidis, John P ; Stefanis, Costas N</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c548t-878201f65d3536028edde64bfc17c209be58b37cfc285a487766a3e39fe118743</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2007</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Adult and adolescent clinical studies</topic><topic>Alleles</topic><topic>Biological and medical sciences</topic><topic>Carrier Proteins - genetics</topic><topic>Carrier Proteins - physiology</topic><topic>Cognition</topic><topic>Cognition - physiology</topic><topic>DAAO</topic><topic>DAOA/G32</topic><topic>DNA - genetics</topic><topic>DTNBP1</topic><topic>Dysbindin</topic><topic>Dystrophin-Associated Proteins</topic><topic>endophenotype</topic><topic>Genotype</topic><topic>Haplotypes</topic><topic>Humans</topic><topic>Intelligence Tests</topic><topic>Linkage Disequilibrium - genetics</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Neuregulin-1 - genetics</topic><topic>Neuregulin-1 - physiology</topic><topic>Neuropsychological Tests</topic><topic>NRG1</topic><topic>Personality disorders</topic><topic>Personality Tests</topic><topic>Phenotype</topic><topic>Polymorphism, Single Nucleotide</topic><topic>Population</topic><topic>Psychiatry</topic><topic>Psychology. Psychoanalysis. Psychiatry</topic><topic>Psychopathology. Psychiatry</topic><topic>Psychoses</topic><topic>Risk</topic><topic>Schizophrenia</topic><topic>Schizophrenia - genetics</topic><topic>Schizophrenic Psychology</topic><topic>Schizotypal Personality Disorder - genetics</topic><topic>Schizotypal Personality Disorder - psychology</topic><topic>schizotypy</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Stefanis, Nicholas C</creatorcontrib><creatorcontrib>Trikalinos, Thomas A</creatorcontrib><creatorcontrib>Avramopoulos, Dimitrios</creatorcontrib><creatorcontrib>Smyrnis, Nikos</creatorcontrib><creatorcontrib>Evdokimidis, Ioannis</creatorcontrib><creatorcontrib>Ntzani, Evangelia E</creatorcontrib><creatorcontrib>Ioannidis, John P</creatorcontrib><creatorcontrib>Stefanis, Costas N</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><jtitle>Biological psychiatry (1969)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Stefanis, Nicholas C</au><au>Trikalinos, Thomas A</au><au>Avramopoulos, Dimitrios</au><au>Smyrnis, Nikos</au><au>Evdokimidis, Ioannis</au><au>Ntzani, Evangelia E</au><au>Ioannidis, John P</au><au>Stefanis, Costas N</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Impact of Schizophrenia Candidate Genes on Schizotypy and Cognitive Endophenotypes at the Population Level</atitle><jtitle>Biological psychiatry (1969)</jtitle><addtitle>Biol Psychiatry</addtitle><date>2007-10-01</date><risdate>2007</risdate><volume>62</volume><issue>7</issue><spage>784</spage><epage>792</epage><pages>784-792</pages><issn>0006-3223</issn><eissn>1873-2402</eissn><coden>BIPCBF</coden><abstract>Background Aspects of cognitive function and schizotypy have been proposed as potential endophenotypes for schizophrenia. It is unknown whether the expression of these endophenotypes at the population level is modulated by the genetic variability of candidate susceptibility genes for schizophrenia. Methods We examined the potential impact of 18 single nucleotide polymorphisms (SNPs) within the DTNBP1 , NRG1 , DAOA/G32 , and DAAO genes, on cognition and self-rated schizotypy, in a representative population of 2243 young male military conscripts. Single SNP and haplotype associations were evaluated. Results The DTNBP1 SNPs rs2619522 and rs760761 exhibited several single marker associations, the minor alleles being associated with lower attention capacity but also a decrease in positive and paranoid schizotypy scores. The DTNBP1 haplotype load had borderline associations with nonverbal IQ, paranoid schizotypy, and sustained attention. For individual NRG1 polymorphisms, isolated but weak signals of association were noted with sustained attention and working memory but not schizotypy. The risk allele of functional SNP8NRG243177 was associated with reduced spatial working memory capacity. An isolated effect of DAAO haplotype variability was noted on negative and disorganization schizotypy. No convincing association of DAOA/G32 variability was detected. Conclusions The DTNBP1 and, less so, NRG1 and DAAO variants might exert gene-specific modulating effects on schizophrenia endophenotypes at the population level.</abstract><cop>New York, NY</cop><pub>Elsevier Inc</pub><pmid>17336946</pmid><doi>10.1016/j.biopsych.2006.11.015</doi><tpages>9</tpages></addata></record> |
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subjects | Adolescent Adult Adult and adolescent clinical studies Alleles Biological and medical sciences Carrier Proteins - genetics Carrier Proteins - physiology Cognition Cognition - physiology DAAO DAOA/G32 DNA - genetics DTNBP1 Dysbindin Dystrophin-Associated Proteins endophenotype Genotype Haplotypes Humans Intelligence Tests Linkage Disequilibrium - genetics Male Medical sciences Neuregulin-1 - genetics Neuregulin-1 - physiology Neuropsychological Tests NRG1 Personality disorders Personality Tests Phenotype Polymorphism, Single Nucleotide Population Psychiatry Psychology. Psychoanalysis. Psychiatry Psychopathology. Psychiatry Psychoses Risk Schizophrenia Schizophrenia - genetics Schizophrenic Psychology Schizotypal Personality Disorder - genetics Schizotypal Personality Disorder - psychology schizotypy |
title | Impact of Schizophrenia Candidate Genes on Schizotypy and Cognitive Endophenotypes at the Population Level |
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