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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Veröffentlicht in:Biological psychiatry (1969) 2007-10, Vol.62 (7), p.784-792
Hauptverfasser: Stefanis, Nicholas C, Trikalinos, Thomas A, Avramopoulos, Dimitrios, Smyrnis, Nikos, Evdokimidis, Ioannis, Ntzani, Evangelia E, Ioannidis, John P, Stefanis, Costas N
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container_end_page 792
container_issue 7
container_start_page 784
container_title Biological psychiatry (1969)
container_volume 62
creator Stefanis, Nicholas C
Trikalinos, Thomas A
Avramopoulos, Dimitrios
Smyrnis, Nikos
Evdokimidis, Ioannis
Ntzani, Evangelia E
Ioannidis, John P
Stefanis, Costas N
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. 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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><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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