Cortical Surfaces Mediate the Relationship Between Polygenic Scores for Intelligence and General Intelligence
Abstract Recent large-scale, genome-wide association studies (GWAS) have identified hundreds of genetic loci associated with general intelligence. The cumulative influence of these loci on brain structure is unknown. We examined if cortical morphology mediates the relationship between GWAS-derived p...
Gespeichert in:
| Veröffentlicht in: | Cerebral cortex (New York, N.Y. 1991) N.Y. 1991), 2020-04, Vol.30 (4), p.2708-2719 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 2719 |
|---|---|
| container_issue | 4 |
| container_start_page | 2708 |
| container_title | Cerebral cortex (New York, N.Y. 1991) |
| container_volume | 30 |
| creator | Lett, Tristram A Vogel, Bob O Ripke, Stephan Wackerhagen, Carolin Erk, Susanne Awasthi, Swapnil Trubetskoy, Vassily Brandl, Eva J Mohnke, Sebastian Veer, Ilya M Nöthen, Markus M Rietschel, Marcella Degenhardt, Franziska Romanczuk-Seiferth, Nina Witt, Stephanie H Banaschewski, Tobias Bokde, Arun L W Büchel, Christian Quinlan, Erin B Desrivières, Sylvane Flor, Herta Frouin, Vincent Garavan, Hugh Gowland, Penny Ittermann, Bernd Martinot, Jean-Luc Martinot, Marie-Laure Paillère Nees, Frauke Papadopoulos-Orfanos, Dimitri Paus, Tomáš Poustka, Luise Fröhner, Juliane H Smolka, Michael N Whelan, Robert Schumann, Gunter Tost, Heike Meyer-Lindenberg, Andreas Heinz, Andreas Walter, Henrik |
| description | Abstract
Recent large-scale, genome-wide association studies (GWAS) have identified hundreds of genetic loci associated with general intelligence. The cumulative influence of these loci on brain structure is unknown. We examined if cortical morphology mediates the relationship between GWAS-derived polygenic scores for intelligence (PSi) and g-factor. Using the effect sizes from one of the largest GWAS meta-analysis on general intelligence to date, PSi were calculated among 10 P value thresholds. PSi were assessed for the association with g-factor performance, cortical thickness (CT), and surface area (SA) in two large imaging-genetics samples (IMAGEN N = 1651; IntegraMooDS N = 742). PSi explained up to 5.1% of the variance of g-factor in IMAGEN (F1,1640 = 12.2–94.3; P |
| doi_str_mv | 10.1093/cercor/bhz270 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7175009</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><oup_id>10.1093/cercor/bhz270</oup_id><sourcerecordid>2325308237</sourcerecordid><originalsourceid>FETCH-LOGICAL-c350t-398e7db9287d44372106db827473b023f099e03cbdd8ca73ba4cb8cb2474f55f3</originalsourceid><addsrcrecordid>eNqFUclOxDAMjRCIZeDIFeXIpZCtpL0gwYhNAoFYzlGaukxQJxmSFDR8PUHDeuJky35-z_ZDaJuSPUpqvm8gGB_2m8kbk2QJrVNxQApG63o550TIgjNK19BGjE-EUMlKtorWOK1YxWqxjqZjH5I1usd3Q-i0gYivoLU6AU4TwLfQ62S9ixM7w8eQXgEcvvH9_BGcNfguS-eJzgd84RL0vc11A1i7Fp-Bg5B5fzc20Uqn-whbn3GEHk5P7sfnxeX12cX46LIwvCSp4HUFsm1qVslWCC4ZJQdtUzEpJG8I4x2payDcNG1bGZ1rWpimMg0TUnRl2fEROlzwzoZmCq0Bl_IqahbsVIe58tqqvx1nJ-rRvyhJZUnyW0do95Mg-OcBYlJTG02-QzvwQ1SMs5KTinGZocUCaoKPMUD3LUOJ-rBILSxSC4syfuf3bt_oL09-tP0w-4frHff4n0A</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2325308237</pqid></control><display><type>article</type><title>Cortical Surfaces Mediate the Relationship Between Polygenic Scores for Intelligence and General Intelligence</title><source>MEDLINE</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>Oxford University Press Journals All Titles (1996-Current)</source><source>Alma/SFX Local Collection</source><creator>Lett, Tristram A ; Vogel, Bob O ; Ripke, Stephan ; Wackerhagen, Carolin ; Erk, Susanne ; Awasthi, Swapnil ; Trubetskoy, Vassily ; Brandl, Eva J ; Mohnke, Sebastian ; Veer, Ilya M ; Nöthen, Markus M ; Rietschel, Marcella ; Degenhardt, Franziska ; Romanczuk-Seiferth, Nina ; Witt, Stephanie H ; Banaschewski, Tobias ; Bokde, Arun L W ; Büchel, Christian ; Quinlan, Erin B ; Desrivières, Sylvane ; Flor, Herta ; Frouin, Vincent ; Garavan, Hugh ; Gowland, Penny ; Ittermann, Bernd ; Martinot, Jean-Luc ; Martinot, Marie-Laure Paillère ; Nees, Frauke ; Papadopoulos-Orfanos, Dimitri ; Paus, Tomáš ; Poustka, Luise ; Fröhner, Juliane H ; Smolka, Michael N ; Whelan, Robert ; Schumann, Gunter ; Tost, Heike ; Meyer-Lindenberg, Andreas ; Heinz, Andreas ; Walter, Henrik</creator><creatorcontrib>Lett, Tristram A ; Vogel, Bob O ; Ripke, Stephan ; Wackerhagen, Carolin ; Erk, Susanne ; Awasthi, Swapnil ; Trubetskoy, Vassily ; Brandl, Eva J ; Mohnke, Sebastian ; Veer, Ilya M ; Nöthen, Markus M ; Rietschel, Marcella ; Degenhardt, Franziska ; Romanczuk-Seiferth, Nina ; Witt, Stephanie H ; Banaschewski, Tobias ; Bokde, Arun L W ; Büchel, Christian ; Quinlan, Erin B ; Desrivières, Sylvane ; Flor, Herta ; Frouin, Vincent ; Garavan, Hugh ; Gowland, Penny ; Ittermann, Bernd ; Martinot, Jean-Luc ; Martinot, Marie-Laure Paillère ; Nees, Frauke ; Papadopoulos-Orfanos, Dimitri ; Paus, Tomáš ; Poustka, Luise ; Fröhner, Juliane H ; Smolka, Michael N ; Whelan, Robert ; Schumann, Gunter ; Tost, Heike ; Meyer-Lindenberg, Andreas ; Heinz, Andreas ; Walter, Henrik ; IMAGEN consortium ; IMAGEN consortium</creatorcontrib><description>Abstract
Recent large-scale, genome-wide association studies (GWAS) have identified hundreds of genetic loci associated with general intelligence. The cumulative influence of these loci on brain structure is unknown. We examined if cortical morphology mediates the relationship between GWAS-derived polygenic scores for intelligence (PSi) and g-factor. Using the effect sizes from one of the largest GWAS meta-analysis on general intelligence to date, PSi were calculated among 10 P value thresholds. PSi were assessed for the association with g-factor performance, cortical thickness (CT), and surface area (SA) in two large imaging-genetics samples (IMAGEN N = 1651; IntegraMooDS N = 742). PSi explained up to 5.1% of the variance of g-factor in IMAGEN (F1,1640 = 12.2–94.3; P < 0.005), and up to 3.0% in IntegraMooDS (F1,725 = 10.0–21.0; P < 0.005). The association between polygenic scores and g-factor was partially mediated by SA and CT in prefrontal, anterior cingulate, insula, and medial temporal cortices in both samples (PFWER-corrected < 0.005). The variance explained by mediation was up to 0.75% in IMAGEN and 0.77% in IntegraMooDS. Our results provide evidence that cumulative genetic load influences g-factor via cortical structure. The consistency of our results across samples suggests that cortex morphology could be a novel potential biomarker for neurocognitive dysfunction that is among the most intractable psychiatric symptoms.</description><identifier>ISSN: 1047-3211</identifier><identifier>ISSN: 1460-2199</identifier><identifier>EISSN: 1460-2199</identifier><identifier>DOI: 10.1093/cercor/bhz270</identifier><identifier>PMID: 31828294</identifier><language>eng</language><publisher>United States: Oxford University Press</publisher><subject>Adolescent ; Cerebral Cortex - diagnostic imaging ; Cerebral Cortex - physiology ; Female ; Genome-Wide Association Study - methods ; Humans ; Intelligence - physiology ; Longitudinal Studies ; Male ; Multifactorial Inheritance - physiology ; Original</subject><ispartof>Cerebral cortex (New York, N.Y. 1991), 2020-04, Vol.30 (4), p.2708-2719</ispartof><rights>The Author(s) 2019. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com. 2019</rights><rights>The Author(s) 2019. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c350t-398e7db9287d44372106db827473b023f099e03cbdd8ca73ba4cb8cb2474f55f3</citedby><cites>FETCH-LOGICAL-c350t-398e7db9287d44372106db827473b023f099e03cbdd8ca73ba4cb8cb2474f55f3</cites><orcidid>0000-0002-8097-1493</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,1584,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31828294$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lett, Tristram A</creatorcontrib><creatorcontrib>Vogel, Bob O</creatorcontrib><creatorcontrib>Ripke, Stephan</creatorcontrib><creatorcontrib>Wackerhagen, Carolin</creatorcontrib><creatorcontrib>Erk, Susanne</creatorcontrib><creatorcontrib>Awasthi, Swapnil</creatorcontrib><creatorcontrib>Trubetskoy, Vassily</creatorcontrib><creatorcontrib>Brandl, Eva J</creatorcontrib><creatorcontrib>Mohnke, Sebastian</creatorcontrib><creatorcontrib>Veer, Ilya M</creatorcontrib><creatorcontrib>Nöthen, Markus M</creatorcontrib><creatorcontrib>Rietschel, Marcella</creatorcontrib><creatorcontrib>Degenhardt, Franziska</creatorcontrib><creatorcontrib>Romanczuk-Seiferth, Nina</creatorcontrib><creatorcontrib>Witt, Stephanie H</creatorcontrib><creatorcontrib>Banaschewski, Tobias</creatorcontrib><creatorcontrib>Bokde, Arun L W</creatorcontrib><creatorcontrib>Büchel, Christian</creatorcontrib><creatorcontrib>Quinlan, Erin B</creatorcontrib><creatorcontrib>Desrivières, Sylvane</creatorcontrib><creatorcontrib>Flor, Herta</creatorcontrib><creatorcontrib>Frouin, Vincent</creatorcontrib><creatorcontrib>Garavan, Hugh</creatorcontrib><creatorcontrib>Gowland, Penny</creatorcontrib><creatorcontrib>Ittermann, Bernd</creatorcontrib><creatorcontrib>Martinot, Jean-Luc</creatorcontrib><creatorcontrib>Martinot, Marie-Laure Paillère</creatorcontrib><creatorcontrib>Nees, Frauke</creatorcontrib><creatorcontrib>Papadopoulos-Orfanos, Dimitri</creatorcontrib><creatorcontrib>Paus, Tomáš</creatorcontrib><creatorcontrib>Poustka, Luise</creatorcontrib><creatorcontrib>Fröhner, Juliane H</creatorcontrib><creatorcontrib>Smolka, Michael N</creatorcontrib><creatorcontrib>Whelan, Robert</creatorcontrib><creatorcontrib>Schumann, Gunter</creatorcontrib><creatorcontrib>Tost, Heike</creatorcontrib><creatorcontrib>Meyer-Lindenberg, Andreas</creatorcontrib><creatorcontrib>Heinz, Andreas</creatorcontrib><creatorcontrib>Walter, Henrik</creatorcontrib><creatorcontrib>IMAGEN consortium</creatorcontrib><creatorcontrib>IMAGEN consortium</creatorcontrib><title>Cortical Surfaces Mediate the Relationship Between Polygenic Scores for Intelligence and General Intelligence</title><title>Cerebral cortex (New York, N.Y. 1991)</title><addtitle>Cereb Cortex</addtitle><description>Abstract
Recent large-scale, genome-wide association studies (GWAS) have identified hundreds of genetic loci associated with general intelligence. The cumulative influence of these loci on brain structure is unknown. We examined if cortical morphology mediates the relationship between GWAS-derived polygenic scores for intelligence (PSi) and g-factor. Using the effect sizes from one of the largest GWAS meta-analysis on general intelligence to date, PSi were calculated among 10 P value thresholds. PSi were assessed for the association with g-factor performance, cortical thickness (CT), and surface area (SA) in two large imaging-genetics samples (IMAGEN N = 1651; IntegraMooDS N = 742). PSi explained up to 5.1% of the variance of g-factor in IMAGEN (F1,1640 = 12.2–94.3; P < 0.005), and up to 3.0% in IntegraMooDS (F1,725 = 10.0–21.0; P < 0.005). The association between polygenic scores and g-factor was partially mediated by SA and CT in prefrontal, anterior cingulate, insula, and medial temporal cortices in both samples (PFWER-corrected < 0.005). The variance explained by mediation was up to 0.75% in IMAGEN and 0.77% in IntegraMooDS. Our results provide evidence that cumulative genetic load influences g-factor via cortical structure. The consistency of our results across samples suggests that cortex morphology could be a novel potential biomarker for neurocognitive dysfunction that is among the most intractable psychiatric symptoms.</description><subject>Adolescent</subject><subject>Cerebral Cortex - diagnostic imaging</subject><subject>Cerebral Cortex - physiology</subject><subject>Female</subject><subject>Genome-Wide Association Study - methods</subject><subject>Humans</subject><subject>Intelligence - physiology</subject><subject>Longitudinal Studies</subject><subject>Male</subject><subject>Multifactorial Inheritance - physiology</subject><subject>Original</subject><issn>1047-3211</issn><issn>1460-2199</issn><issn>1460-2199</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFUclOxDAMjRCIZeDIFeXIpZCtpL0gwYhNAoFYzlGaukxQJxmSFDR8PUHDeuJky35-z_ZDaJuSPUpqvm8gGB_2m8kbk2QJrVNxQApG63o550TIgjNK19BGjE-EUMlKtorWOK1YxWqxjqZjH5I1usd3Q-i0gYivoLU6AU4TwLfQ62S9ixM7w8eQXgEcvvH9_BGcNfguS-eJzgd84RL0vc11A1i7Fp-Bg5B5fzc20Uqn-whbn3GEHk5P7sfnxeX12cX46LIwvCSp4HUFsm1qVslWCC4ZJQdtUzEpJG8I4x2payDcNG1bGZ1rWpimMg0TUnRl2fEROlzwzoZmCq0Bl_IqahbsVIe58tqqvx1nJ-rRvyhJZUnyW0do95Mg-OcBYlJTG02-QzvwQ1SMs5KTinGZocUCaoKPMUD3LUOJ-rBILSxSC4syfuf3bt_oL09-tP0w-4frHff4n0A</recordid><startdate>20200414</startdate><enddate>20200414</enddate><creator>Lett, Tristram A</creator><creator>Vogel, Bob O</creator><creator>Ripke, Stephan</creator><creator>Wackerhagen, Carolin</creator><creator>Erk, Susanne</creator><creator>Awasthi, Swapnil</creator><creator>Trubetskoy, Vassily</creator><creator>Brandl, Eva J</creator><creator>Mohnke, Sebastian</creator><creator>Veer, Ilya M</creator><creator>Nöthen, Markus M</creator><creator>Rietschel, Marcella</creator><creator>Degenhardt, Franziska</creator><creator>Romanczuk-Seiferth, Nina</creator><creator>Witt, Stephanie H</creator><creator>Banaschewski, Tobias</creator><creator>Bokde, Arun L W</creator><creator>Büchel, Christian</creator><creator>Quinlan, Erin B</creator><creator>Desrivières, Sylvane</creator><creator>Flor, Herta</creator><creator>Frouin, Vincent</creator><creator>Garavan, Hugh</creator><creator>Gowland, Penny</creator><creator>Ittermann, Bernd</creator><creator>Martinot, Jean-Luc</creator><creator>Martinot, Marie-Laure Paillère</creator><creator>Nees, Frauke</creator><creator>Papadopoulos-Orfanos, Dimitri</creator><creator>Paus, Tomáš</creator><creator>Poustka, Luise</creator><creator>Fröhner, Juliane H</creator><creator>Smolka, Michael N</creator><creator>Whelan, Robert</creator><creator>Schumann, Gunter</creator><creator>Tost, Heike</creator><creator>Meyer-Lindenberg, Andreas</creator><creator>Heinz, Andreas</creator><creator>Walter, Henrik</creator><general>Oxford University Press</general><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>5PM</scope><orcidid>https://orcid.org/0000-0002-8097-1493</orcidid></search><sort><creationdate>20200414</creationdate><title>Cortical Surfaces Mediate the Relationship Between Polygenic Scores for Intelligence and General Intelligence</title><author>Lett, Tristram A ; Vogel, Bob O ; Ripke, Stephan ; Wackerhagen, Carolin ; Erk, Susanne ; Awasthi, Swapnil ; Trubetskoy, Vassily ; Brandl, Eva J ; Mohnke, Sebastian ; Veer, Ilya M ; Nöthen, Markus M ; Rietschel, Marcella ; Degenhardt, Franziska ; Romanczuk-Seiferth, Nina ; Witt, Stephanie H ; Banaschewski, Tobias ; Bokde, Arun L W ; Büchel, Christian ; Quinlan, Erin B ; Desrivières, Sylvane ; Flor, Herta ; Frouin, Vincent ; Garavan, Hugh ; Gowland, Penny ; Ittermann, Bernd ; Martinot, Jean-Luc ; Martinot, Marie-Laure Paillère ; Nees, Frauke ; Papadopoulos-Orfanos, Dimitri ; Paus, Tomáš ; Poustka, Luise ; Fröhner, Juliane H ; Smolka, Michael N ; Whelan, Robert ; Schumann, Gunter ; Tost, Heike ; Meyer-Lindenberg, Andreas ; Heinz, Andreas ; Walter, Henrik</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c350t-398e7db9287d44372106db827473b023f099e03cbdd8ca73ba4cb8cb2474f55f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Adolescent</topic><topic>Cerebral Cortex - diagnostic imaging</topic><topic>Cerebral Cortex - physiology</topic><topic>Female</topic><topic>Genome-Wide Association Study - methods</topic><topic>Humans</topic><topic>Intelligence - physiology</topic><topic>Longitudinal Studies</topic><topic>Male</topic><topic>Multifactorial Inheritance - physiology</topic><topic>Original</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lett, Tristram A</creatorcontrib><creatorcontrib>Vogel, Bob O</creatorcontrib><creatorcontrib>Ripke, Stephan</creatorcontrib><creatorcontrib>Wackerhagen, Carolin</creatorcontrib><creatorcontrib>Erk, Susanne</creatorcontrib><creatorcontrib>Awasthi, Swapnil</creatorcontrib><creatorcontrib>Trubetskoy, Vassily</creatorcontrib><creatorcontrib>Brandl, Eva J</creatorcontrib><creatorcontrib>Mohnke, Sebastian</creatorcontrib><creatorcontrib>Veer, Ilya M</creatorcontrib><creatorcontrib>Nöthen, Markus M</creatorcontrib><creatorcontrib>Rietschel, Marcella</creatorcontrib><creatorcontrib>Degenhardt, Franziska</creatorcontrib><creatorcontrib>Romanczuk-Seiferth, Nina</creatorcontrib><creatorcontrib>Witt, Stephanie H</creatorcontrib><creatorcontrib>Banaschewski, Tobias</creatorcontrib><creatorcontrib>Bokde, Arun L W</creatorcontrib><creatorcontrib>Büchel, Christian</creatorcontrib><creatorcontrib>Quinlan, Erin B</creatorcontrib><creatorcontrib>Desrivières, Sylvane</creatorcontrib><creatorcontrib>Flor, Herta</creatorcontrib><creatorcontrib>Frouin, Vincent</creatorcontrib><creatorcontrib>Garavan, Hugh</creatorcontrib><creatorcontrib>Gowland, Penny</creatorcontrib><creatorcontrib>Ittermann, Bernd</creatorcontrib><creatorcontrib>Martinot, Jean-Luc</creatorcontrib><creatorcontrib>Martinot, Marie-Laure Paillère</creatorcontrib><creatorcontrib>Nees, Frauke</creatorcontrib><creatorcontrib>Papadopoulos-Orfanos, Dimitri</creatorcontrib><creatorcontrib>Paus, Tomáš</creatorcontrib><creatorcontrib>Poustka, Luise</creatorcontrib><creatorcontrib>Fröhner, Juliane H</creatorcontrib><creatorcontrib>Smolka, Michael N</creatorcontrib><creatorcontrib>Whelan, Robert</creatorcontrib><creatorcontrib>Schumann, Gunter</creatorcontrib><creatorcontrib>Tost, Heike</creatorcontrib><creatorcontrib>Meyer-Lindenberg, Andreas</creatorcontrib><creatorcontrib>Heinz, Andreas</creatorcontrib><creatorcontrib>Walter, Henrik</creatorcontrib><creatorcontrib>IMAGEN consortium</creatorcontrib><creatorcontrib>IMAGEN consortium</creatorcontrib><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>PubMed Central (Full Participant titles)</collection><jtitle>Cerebral cortex (New York, N.Y. 1991)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lett, Tristram A</au><au>Vogel, Bob O</au><au>Ripke, Stephan</au><au>Wackerhagen, Carolin</au><au>Erk, Susanne</au><au>Awasthi, Swapnil</au><au>Trubetskoy, Vassily</au><au>Brandl, Eva J</au><au>Mohnke, Sebastian</au><au>Veer, Ilya M</au><au>Nöthen, Markus M</au><au>Rietschel, Marcella</au><au>Degenhardt, Franziska</au><au>Romanczuk-Seiferth, Nina</au><au>Witt, Stephanie H</au><au>Banaschewski, Tobias</au><au>Bokde, Arun L W</au><au>Büchel, Christian</au><au>Quinlan, Erin B</au><au>Desrivières, Sylvane</au><au>Flor, Herta</au><au>Frouin, Vincent</au><au>Garavan, Hugh</au><au>Gowland, Penny</au><au>Ittermann, Bernd</au><au>Martinot, Jean-Luc</au><au>Martinot, Marie-Laure Paillère</au><au>Nees, Frauke</au><au>Papadopoulos-Orfanos, Dimitri</au><au>Paus, Tomáš</au><au>Poustka, Luise</au><au>Fröhner, Juliane H</au><au>Smolka, Michael N</au><au>Whelan, Robert</au><au>Schumann, Gunter</au><au>Tost, Heike</au><au>Meyer-Lindenberg, Andreas</au><au>Heinz, Andreas</au><au>Walter, Henrik</au><aucorp>IMAGEN consortium</aucorp><aucorp>IMAGEN consortium</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Cortical Surfaces Mediate the Relationship Between Polygenic Scores for Intelligence and General Intelligence</atitle><jtitle>Cerebral cortex (New York, N.Y. 1991)</jtitle><addtitle>Cereb Cortex</addtitle><date>2020-04-14</date><risdate>2020</risdate><volume>30</volume><issue>4</issue><spage>2708</spage><epage>2719</epage><pages>2708-2719</pages><issn>1047-3211</issn><issn>1460-2199</issn><eissn>1460-2199</eissn><abstract>Abstract
Recent large-scale, genome-wide association studies (GWAS) have identified hundreds of genetic loci associated with general intelligence. The cumulative influence of these loci on brain structure is unknown. We examined if cortical morphology mediates the relationship between GWAS-derived polygenic scores for intelligence (PSi) and g-factor. Using the effect sizes from one of the largest GWAS meta-analysis on general intelligence to date, PSi were calculated among 10 P value thresholds. PSi were assessed for the association with g-factor performance, cortical thickness (CT), and surface area (SA) in two large imaging-genetics samples (IMAGEN N = 1651; IntegraMooDS N = 742). PSi explained up to 5.1% of the variance of g-factor in IMAGEN (F1,1640 = 12.2–94.3; P < 0.005), and up to 3.0% in IntegraMooDS (F1,725 = 10.0–21.0; P < 0.005). The association between polygenic scores and g-factor was partially mediated by SA and CT in prefrontal, anterior cingulate, insula, and medial temporal cortices in both samples (PFWER-corrected < 0.005). The variance explained by mediation was up to 0.75% in IMAGEN and 0.77% in IntegraMooDS. Our results provide evidence that cumulative genetic load influences g-factor via cortical structure. The consistency of our results across samples suggests that cortex morphology could be a novel potential biomarker for neurocognitive dysfunction that is among the most intractable psychiatric symptoms.</abstract><cop>United States</cop><pub>Oxford University Press</pub><pmid>31828294</pmid><doi>10.1093/cercor/bhz270</doi><tpages>12</tpages><orcidid>https://orcid.org/0000-0002-8097-1493</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1047-3211 |
| ispartof | Cerebral cortex (New York, N.Y. 1991), 2020-04, Vol.30 (4), p.2708-2719 |
| issn | 1047-3211 1460-2199 1460-2199 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7175009 |
| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Oxford University Press Journals All Titles (1996-Current); Alma/SFX Local Collection |
| subjects | Adolescent Cerebral Cortex - diagnostic imaging Cerebral Cortex - physiology Female Genome-Wide Association Study - methods Humans Intelligence - physiology Longitudinal Studies Male Multifactorial Inheritance - physiology Original |
| title | Cortical Surfaces Mediate the Relationship Between Polygenic Scores for Intelligence and General Intelligence |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-08T02%3A36%3A23IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Cortical%20Surfaces%20Mediate%20the%20Relationship%20Between%20Polygenic%20Scores%20for%20Intelligence%20and%20General%20Intelligence&rft.jtitle=Cerebral%20cortex%20(New%20York,%20N.Y.%201991)&rft.au=Lett,%20Tristram%20A&rft.aucorp=IMAGEN%20consortium&rft.date=2020-04-14&rft.volume=30&rft.issue=4&rft.spage=2708&rft.epage=2719&rft.pages=2708-2719&rft.issn=1047-3211&rft.eissn=1460-2199&rft_id=info:doi/10.1093/cercor/bhz270&rft_dat=%3Cproquest_pubme%3E2325308237%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2325308237&rft_id=info:pmid/31828294&rft_oup_id=10.1093/cercor/bhz270&rfr_iscdi=true |