Analysis of schizophrenia-related genes and electrophysiological measures reveals ZNF804A association with amplitude of P300b elicited by novel sounds
Several genes have recently been identified as risk factors for schizophrenia (SZ) by genome-wide association studies (GWAS), including ZNF804A which is thought to function in transcriptional regulation. However, the downstream pathophysiological changes that these genes confer remain to be elucidat...
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| Veröffentlicht in: | Translational psychiatry 2014-01, Vol.4 (1), p.e346-e346 |
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| creator | del Re, E C Bergen, S E Mesholam-Gately, R I Niznikiewicz, M A Goldstein, J M Woo, T U Shenton, M E Seidman, L J McCarley, R W Petryshen, T L |
| description | Several genes have recently been identified as risk factors for schizophrenia (SZ) by genome-wide association studies (GWAS), including ZNF804A which is thought to function in transcriptional regulation. However, the downstream pathophysiological changes that these genes confer remain to be elucidated. In 143 subjects (68 clinical high risk, first episode or chronic cases; 75 controls), we examined the association between 21 genetic markers previously identified by SZ GWAS or associated with putative intermediate phenotypes of SZ against three event-related potential (ERP) measures: mismatch negativity (MMN), amplitude of P300 during an auditory oddball task, and P300 amplitude during an auditory novelty oddball task. Controlling for age and sex, significant genetic association surpassing Bonferroni correction was detected between ZNF804A marker rs1344706 and P300 amplitude elicited by novel sounds (beta=4.38,
P
=1.03 × 10
−4
), which is thought to index orienting of attention to unexpected, salient stimuli. Subsequent analyses revealed that the association was driven by the control subjects (beta=6.35,
P
=9.08 × 10
−5
), and that the risk allele was correlated with higher novel P300b amplitude, in contrast to the significantly lower amplitude observed in cases compared to controls. Novel P300b amplitude was significantly correlated with a neurocognitive measure of auditory attention under interference conditions, suggesting a relationship between novel P300b amplitude and higher-order attentional processes. Our results suggest pleiotropic effects of ZNF804A on risk for SZ and neural mechanisms that are indexed by the novel P300b ERP component. |
| doi_str_mv | 10.1038/tp.2013.117 |
| format | Article |
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P
=1.03 × 10
−4
), which is thought to index orienting of attention to unexpected, salient stimuli. Subsequent analyses revealed that the association was driven by the control subjects (beta=6.35,
P
=9.08 × 10
−5
), and that the risk allele was correlated with higher novel P300b amplitude, in contrast to the significantly lower amplitude observed in cases compared to controls. Novel P300b amplitude was significantly correlated with a neurocognitive measure of auditory attention under interference conditions, suggesting a relationship between novel P300b amplitude and higher-order attentional processes. Our results suggest pleiotropic effects of ZNF804A on risk for SZ and neural mechanisms that are indexed by the novel P300b ERP component.</description><identifier>ISSN: 2158-3188</identifier><identifier>EISSN: 2158-3188</identifier><identifier>DOI: 10.1038/tp.2013.117</identifier><identifier>PMID: 24424392</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>631/1647/1453 ; 692/420/2489/144 ; 692/699/476/1799 ; Adolescent ; Adult ; Attention - physiology ; Behavioral Sciences ; Biological Psychology ; Biomarkers ; Electroencephalography ; Event-Related Potentials, P300 - genetics ; Event-Related Potentials, P300 - physiology ; Evoked Potentials, Auditory - genetics ; Evoked Potentials, Auditory - physiology ; Female ; Genetic Predisposition to Disease - genetics ; Humans ; Kruppel-Like Transcription Factors - genetics ; Male ; Medicine ; Medicine & Public Health ; Neurosciences ; Original ; original-article ; Pharmacotherapy ; Psychiatry ; Schizophrenia - genetics ; Schizophrenia - physiopathology ; Young Adult</subject><ispartof>Translational psychiatry, 2014-01, Vol.4 (1), p.e346-e346</ispartof><rights>The Author(s) 2014</rights><rights>Copyright Nature Publishing Group Jan 2014</rights><rights>Copyright © 2014 Macmillan Publishers Limited 2014 Macmillan Publishers Limited</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c484t-a224870f19c53a1619a9b44ef97e8fc21fffd716babcc68d52b72a96c9c532273</citedby><cites>FETCH-LOGICAL-c484t-a224870f19c53a1619a9b44ef97e8fc21fffd716babcc68d52b72a96c9c532273</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3905227/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3905227/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,550,723,776,780,860,881,27901,27902,41096,42165,51551,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24424392$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttp://kipublications.ki.se/Default.aspx?queryparsed=id:129238073$$DView record from Swedish Publication Index$$Hfree_for_read</backlink></links><search><creatorcontrib>del Re, E C</creatorcontrib><creatorcontrib>Bergen, S E</creatorcontrib><creatorcontrib>Mesholam-Gately, R I</creatorcontrib><creatorcontrib>Niznikiewicz, M A</creatorcontrib><creatorcontrib>Goldstein, J M</creatorcontrib><creatorcontrib>Woo, T U</creatorcontrib><creatorcontrib>Shenton, M E</creatorcontrib><creatorcontrib>Seidman, L J</creatorcontrib><creatorcontrib>McCarley, R W</creatorcontrib><creatorcontrib>Petryshen, T L</creatorcontrib><title>Analysis of schizophrenia-related genes and electrophysiological measures reveals ZNF804A association with amplitude of P300b elicited by novel sounds</title><title>Translational psychiatry</title><addtitle>Transl Psychiatry</addtitle><addtitle>Transl Psychiatry</addtitle><description>Several genes have recently been identified as risk factors for schizophrenia (SZ) by genome-wide association studies (GWAS), including ZNF804A which is thought to function in transcriptional regulation. However, the downstream pathophysiological changes that these genes confer remain to be elucidated. In 143 subjects (68 clinical high risk, first episode or chronic cases; 75 controls), we examined the association between 21 genetic markers previously identified by SZ GWAS or associated with putative intermediate phenotypes of SZ against three event-related potential (ERP) measures: mismatch negativity (MMN), amplitude of P300 during an auditory oddball task, and P300 amplitude during an auditory novelty oddball task. Controlling for age and sex, significant genetic association surpassing Bonferroni correction was detected between ZNF804A marker rs1344706 and P300 amplitude elicited by novel sounds (beta=4.38,
P
=1.03 × 10
−4
), which is thought to index orienting of attention to unexpected, salient stimuli. Subsequent analyses revealed that the association was driven by the control subjects (beta=6.35,
P
=9.08 × 10
−5
), and that the risk allele was correlated with higher novel P300b amplitude, in contrast to the significantly lower amplitude observed in cases compared to controls. Novel P300b amplitude was significantly correlated with a neurocognitive measure of auditory attention under interference conditions, suggesting a relationship between novel P300b amplitude and higher-order attentional processes. Our results suggest pleiotropic effects of ZNF804A on risk for SZ and neural mechanisms that are indexed by the novel P300b ERP component.</description><subject>631/1647/1453</subject><subject>692/420/2489/144</subject><subject>692/699/476/1799</subject><subject>Adolescent</subject><subject>Adult</subject><subject>Attention - physiology</subject><subject>Behavioral Sciences</subject><subject>Biological Psychology</subject><subject>Biomarkers</subject><subject>Electroencephalography</subject><subject>Event-Related Potentials, P300 - genetics</subject><subject>Event-Related Potentials, P300 - physiology</subject><subject>Evoked Potentials, Auditory - genetics</subject><subject>Evoked Potentials, Auditory - physiology</subject><subject>Female</subject><subject>Genetic Predisposition to Disease - genetics</subject><subject>Humans</subject><subject>Kruppel-Like Transcription Factors - genetics</subject><subject>Male</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Neurosciences</subject><subject>Original</subject><subject>original-article</subject><subject>Pharmacotherapy</subject><subject>Psychiatry</subject><subject>Schizophrenia - genetics</subject><subject>Schizophrenia - physiopathology</subject><subject>Young Adult</subject><issn>2158-3188</issn><issn>2158-3188</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>D8T</sourceid><recordid>eNptksFu1DAQhiMEolXpiTuyxAWpZLEdJ3YuSKuKFqQKOMCFi-U4k10Xrx1sZ6vlQXjeOtql2iJ88cjzzf-PxlMULwleEFyJd2lcUEyqBSH8SXFKSS3Kigjx9Cg-Kc5jvMX51EwQTp4XJ5QxyqqWnhZ_lk7ZXTQR-QFFvTa__bgO4IwqA1iVoEcrcBCRcj0CCzqFDOQCb_3KaGXRBlScQiYCbEHZiH58vhKYLZGK0WujkvEO3Zm0RmozWpOmHmavrxXGXVY02swm3Q45vwWLop9cH18Uz4asBeeH-6z4fvXh2-XH8ubL9afL5U2pmWCpVJQywfFAWl1XijSkVW3HGAwtBzFoSoZh6DlpOtVp3Yi-ph2nqm30zFPKq7Oi3OvGOxinTo7BbFTYSa-MPDz9zBHIOs-Lt5l_v-dzZgO9BpeCso_KHmecWcuV38qqxfXe8M1BIPhfE8QkNyZqsFY58FOUhLWYN0zUVUZf_4Pe-ink78oUbwmhTW4oUxd7SgcfY4DhoRmC5bwiMo1yXhGZVyTTr477f2D_LkQG3h4GklNuBeHI9D969yTDyO0</recordid><startdate>20140101</startdate><enddate>20140101</enddate><creator>del Re, E C</creator><creator>Bergen, S E</creator><creator>Mesholam-Gately, R I</creator><creator>Niznikiewicz, M A</creator><creator>Goldstein, J M</creator><creator>Woo, T U</creator><creator>Shenton, M E</creator><creator>Seidman, L J</creator><creator>McCarley, R W</creator><creator>Petryshen, T L</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><scope>C6C</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>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope><scope>ADTPV</scope><scope>AOWAS</scope><scope>D8T</scope><scope>ZZAVC</scope></search><sort><creationdate>20140101</creationdate><title>Analysis of schizophrenia-related genes and electrophysiological measures reveals ZNF804A association with amplitude of P300b elicited by novel sounds</title><author>del Re, E C ; Bergen, S E ; Mesholam-Gately, R I ; Niznikiewicz, M A ; Goldstein, J M ; Woo, T U ; Shenton, M E ; Seidman, L J ; McCarley, R W ; Petryshen, T L</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c484t-a224870f19c53a1619a9b44ef97e8fc21fffd716babcc68d52b72a96c9c532273</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>631/1647/1453</topic><topic>692/420/2489/144</topic><topic>692/699/476/1799</topic><topic>Adolescent</topic><topic>Adult</topic><topic>Attention - physiology</topic><topic>Behavioral Sciences</topic><topic>Biological Psychology</topic><topic>Biomarkers</topic><topic>Electroencephalography</topic><topic>Event-Related Potentials, P300 - genetics</topic><topic>Event-Related Potentials, P300 - physiology</topic><topic>Evoked Potentials, Auditory - genetics</topic><topic>Evoked Potentials, Auditory - physiology</topic><topic>Female</topic><topic>Genetic Predisposition to Disease - genetics</topic><topic>Humans</topic><topic>Kruppel-Like Transcription Factors - genetics</topic><topic>Male</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Neurosciences</topic><topic>Original</topic><topic>original-article</topic><topic>Pharmacotherapy</topic><topic>Psychiatry</topic><topic>Schizophrenia - genetics</topic><topic>Schizophrenia - physiopathology</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>del Re, E C</creatorcontrib><creatorcontrib>Bergen, S E</creatorcontrib><creatorcontrib>Mesholam-Gately, R I</creatorcontrib><creatorcontrib>Niznikiewicz, M A</creatorcontrib><creatorcontrib>Goldstein, J M</creatorcontrib><creatorcontrib>Woo, T U</creatorcontrib><creatorcontrib>Shenton, M E</creatorcontrib><creatorcontrib>Seidman, L J</creatorcontrib><creatorcontrib>McCarley, R W</creatorcontrib><creatorcontrib>Petryshen, T L</creatorcontrib><collection>Springer Nature OA Free Journals</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>SwePub</collection><collection>SwePub Articles</collection><collection>SWEPUB Freely available online</collection><collection>SwePub Articles full text</collection><jtitle>Translational psychiatry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>del Re, E C</au><au>Bergen, S E</au><au>Mesholam-Gately, R I</au><au>Niznikiewicz, M A</au><au>Goldstein, J M</au><au>Woo, T U</au><au>Shenton, M E</au><au>Seidman, L J</au><au>McCarley, R W</au><au>Petryshen, T L</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Analysis of schizophrenia-related genes and electrophysiological measures reveals ZNF804A association with amplitude of P300b elicited by novel sounds</atitle><jtitle>Translational psychiatry</jtitle><stitle>Transl Psychiatry</stitle><addtitle>Transl Psychiatry</addtitle><date>2014-01-01</date><risdate>2014</risdate><volume>4</volume><issue>1</issue><spage>e346</spage><epage>e346</epage><pages>e346-e346</pages><issn>2158-3188</issn><eissn>2158-3188</eissn><abstract>Several genes have recently been identified as risk factors for schizophrenia (SZ) by genome-wide association studies (GWAS), including ZNF804A which is thought to function in transcriptional regulation. However, the downstream pathophysiological changes that these genes confer remain to be elucidated. In 143 subjects (68 clinical high risk, first episode or chronic cases; 75 controls), we examined the association between 21 genetic markers previously identified by SZ GWAS or associated with putative intermediate phenotypes of SZ against three event-related potential (ERP) measures: mismatch negativity (MMN), amplitude of P300 during an auditory oddball task, and P300 amplitude during an auditory novelty oddball task. Controlling for age and sex, significant genetic association surpassing Bonferroni correction was detected between ZNF804A marker rs1344706 and P300 amplitude elicited by novel sounds (beta=4.38,
P
=1.03 × 10
−4
), which is thought to index orienting of attention to unexpected, salient stimuli. Subsequent analyses revealed that the association was driven by the control subjects (beta=6.35,
P
=9.08 × 10
−5
), and that the risk allele was correlated with higher novel P300b amplitude, in contrast to the significantly lower amplitude observed in cases compared to controls. Novel P300b amplitude was significantly correlated with a neurocognitive measure of auditory attention under interference conditions, suggesting a relationship between novel P300b amplitude and higher-order attentional processes. Our results suggest pleiotropic effects of ZNF804A on risk for SZ and neural mechanisms that are indexed by the novel P300b ERP component.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>24424392</pmid><doi>10.1038/tp.2013.117</doi><oa>free_for_read</oa></addata></record> |
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| subjects | 631/1647/1453 692/420/2489/144 692/699/476/1799 Adolescent Adult Attention - physiology Behavioral Sciences Biological Psychology Biomarkers Electroencephalography Event-Related Potentials, P300 - genetics Event-Related Potentials, P300 - physiology Evoked Potentials, Auditory - genetics Evoked Potentials, Auditory - physiology Female Genetic Predisposition to Disease - genetics Humans Kruppel-Like Transcription Factors - genetics Male Medicine Medicine & Public Health Neurosciences Original original-article Pharmacotherapy Psychiatry Schizophrenia - genetics Schizophrenia - physiopathology Young Adult |
| title | Analysis of schizophrenia-related genes and electrophysiological measures reveals ZNF804A association with amplitude of P300b elicited by novel sounds |
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