Fine mapping genetic associations between the HLA region and extremely high intelligence
General cognitive ability (intelligence) is one of the most heritable behavioural traits and most predictive of socially important outcomes and health. We hypothesized that some of the missing heritability of IQ might lie hidden in the human leukocyte antigen (HLA) region, which plays a critical rol...
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| Veröffentlicht in: | Scientific reports 2017-01, Vol.7 (1), p.41182-41182, Article 41182 |
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| creator | Zabaneh, Delilah Krapohl, Eva Simpson, Michael A. Miller, Mike B. Iacono, William G. McGue, Matt Putallaz, Martha Lubinski, David Plomin, Robert Breen, Gerome |
| description | General cognitive ability (intelligence) is one of the most heritable behavioural traits and most predictive of socially important outcomes and health. We hypothesized that some of the missing heritability of IQ might lie hidden in the human leukocyte antigen (HLA) region, which plays a critical role in many diseases and traits but is not well tagged in conventional GWAS. Using a uniquely powered design, we investigated whether fine-mapping of the HLA region could narrow the missing heritability gap. Our case-control design included 1,393 cases with extremely high intelligence scores (top 0.0003 of the population equivalent to IQ > 147) and 3,253 unselected population controls. We imputed variants in 200 genes across the HLA region, one SNP (rs444921) reached our criterion for study-wide significance. SNP-based heritability of the HLA variants was small and not significant (h
2
= 0.3%, SE = 0.2%). A polygenic score from the case-control genetic association analysis of SNPs in the HLA region did not significantly predict individual differences in intelligence in an independent unselected sample. We conclude that although genetic variation in the HLA region is important to the aetiology of many disorders, it does not appear to be hiding much of the missing heritability of intelligence. |
| doi_str_mv | 10.1038/srep41182 |
| format | Article |
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2
= 0.3%, SE = 0.2%). A polygenic score from the case-control genetic association analysis of SNPs in the HLA region did not significantly predict individual differences in intelligence in an independent unselected sample. We conclude that although genetic variation in the HLA region is important to the aetiology of many disorders, it does not appear to be hiding much of the missing heritability of intelligence.</description><identifier>ISSN: 2045-2322</identifier><identifier>EISSN: 2045-2322</identifier><identifier>DOI: 10.1038/srep41182</identifier><identifier>PMID: 28117369</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>45 ; 45/43 ; 631/208/1515 ; 631/208/205 ; Association analysis ; Case-Control Studies ; Chromosome Mapping - methods ; Cognitive ability ; Female ; Gene mapping ; Genetic diversity ; Genotype ; Heritability ; Histocompatibility antigen HLA ; HLA Antigens - genetics ; Humanities and Social Sciences ; Humans ; Intelligence ; Intelligence - genetics ; Male ; multidisciplinary ; Multifactorial Inheritance ; Polygenic inheritance ; Polymorphism, Single Nucleotide ; Science ; Science (multidisciplinary) ; Single-nucleotide polymorphism</subject><ispartof>Scientific reports, 2017-01, Vol.7 (1), p.41182-41182, Article 41182</ispartof><rights>The Author(s) 2017</rights><rights>Copyright Nature Publishing Group Jan 2017</rights><rights>Copyright © 2017, The Author(s) 2017 The Author(s)</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c438t-effcb306201be90d1aa675a864a47ccd7001ef4c02da408db211dc541d06a8bc3</citedby><cites>FETCH-LOGICAL-c438t-effcb306201be90d1aa675a864a47ccd7001ef4c02da408db211dc541d06a8bc3</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/PMC5259706/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5259706/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,27924,27925,41120,42189,51576,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28117369$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zabaneh, Delilah</creatorcontrib><creatorcontrib>Krapohl, Eva</creatorcontrib><creatorcontrib>Simpson, Michael A.</creatorcontrib><creatorcontrib>Miller, Mike B.</creatorcontrib><creatorcontrib>Iacono, William G.</creatorcontrib><creatorcontrib>McGue, Matt</creatorcontrib><creatorcontrib>Putallaz, Martha</creatorcontrib><creatorcontrib>Lubinski, David</creatorcontrib><creatorcontrib>Plomin, Robert</creatorcontrib><creatorcontrib>Breen, Gerome</creatorcontrib><title>Fine mapping genetic associations between the HLA region and extremely high intelligence</title><title>Scientific reports</title><addtitle>Sci Rep</addtitle><addtitle>Sci Rep</addtitle><description>General cognitive ability (intelligence) is one of the most heritable behavioural traits and most predictive of socially important outcomes and health. We hypothesized that some of the missing heritability of IQ might lie hidden in the human leukocyte antigen (HLA) region, which plays a critical role in many diseases and traits but is not well tagged in conventional GWAS. Using a uniquely powered design, we investigated whether fine-mapping of the HLA region could narrow the missing heritability gap. Our case-control design included 1,393 cases with extremely high intelligence scores (top 0.0003 of the population equivalent to IQ > 147) and 3,253 unselected population controls. We imputed variants in 200 genes across the HLA region, one SNP (rs444921) reached our criterion for study-wide significance. SNP-based heritability of the HLA variants was small and not significant (h
2
= 0.3%, SE = 0.2%). A polygenic score from the case-control genetic association analysis of SNPs in the HLA region did not significantly predict individual differences in intelligence in an independent unselected sample. We conclude that although genetic variation in the HLA region is important to the aetiology of many disorders, it does not appear to be hiding much of the missing heritability of intelligence.</description><subject>45</subject><subject>45/43</subject><subject>631/208/1515</subject><subject>631/208/205</subject><subject>Association analysis</subject><subject>Case-Control Studies</subject><subject>Chromosome Mapping - methods</subject><subject>Cognitive ability</subject><subject>Female</subject><subject>Gene mapping</subject><subject>Genetic diversity</subject><subject>Genotype</subject><subject>Heritability</subject><subject>Histocompatibility antigen HLA</subject><subject>HLA Antigens - genetics</subject><subject>Humanities and Social Sciences</subject><subject>Humans</subject><subject>Intelligence</subject><subject>Intelligence - genetics</subject><subject>Male</subject><subject>multidisciplinary</subject><subject>Multifactorial Inheritance</subject><subject>Polygenic inheritance</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Science</subject><subject>Science (multidisciplinary)</subject><subject>Single-nucleotide polymorphism</subject><issn>2045-2322</issn><issn>2045-2322</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNplkU1LxDAQhoMoKurBPyABLyqsJmnaJhdBxC9Y8KLgLaTptBtp05pk_fj3RlaXVXNJyDw8M8OL0D4lp5Rk4ix4GDmlgq2hbUZ4PmEZY-sr7y20F8IzSSdnklO5ibaYoLTMCrmNnq6tA9zrcbSuxS04iNZgHcJgrI52cAFXEN8AHI4zwLfTC-yhTf9YuxrDe_TQQ_eBZ7adYesidJ1NFgO7aKPRXYC973sHPV5fPVzeTqb3N3eXF9OJ4ZmIE2gaU2WkYIRWIElNtS7KXIuCa14aU5eEUGi4IazWnIi6YpTWJue0JoUWlcl20PnCO86rHmoDLnrdqdHbXvsPNWirflecnal2eFU5y2VJiiQ4-hb44WUOIareBpP20A6GeVBUFLQgkgmZ0MM_6PMw9y6tlygp80wyliXqeEEZP4SUTrMchhL1FZlaRpbYg9Xpl-RPQAk4WQAhlVwLfqXlP9snsyShPg</recordid><startdate>20170124</startdate><enddate>20170124</enddate><creator>Zabaneh, Delilah</creator><creator>Krapohl, Eva</creator><creator>Simpson, Michael A.</creator><creator>Miller, Mike B.</creator><creator>Iacono, William G.</creator><creator>McGue, Matt</creator><creator>Putallaz, Martha</creator><creator>Lubinski, David</creator><creator>Plomin, Robert</creator><creator>Breen, Gerome</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>88A</scope><scope>88E</scope><scope>88I</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>M7P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20170124</creationdate><title>Fine mapping genetic associations between the HLA region and extremely high intelligence</title><author>Zabaneh, Delilah ; Krapohl, Eva ; Simpson, Michael A. ; Miller, Mike B. ; Iacono, William G. ; McGue, Matt ; Putallaz, Martha ; Lubinski, David ; Plomin, Robert ; Breen, Gerome</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c438t-effcb306201be90d1aa675a864a47ccd7001ef4c02da408db211dc541d06a8bc3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>45</topic><topic>45/43</topic><topic>631/208/1515</topic><topic>631/208/205</topic><topic>Association analysis</topic><topic>Case-Control Studies</topic><topic>Chromosome Mapping - methods</topic><topic>Cognitive ability</topic><topic>Female</topic><topic>Gene mapping</topic><topic>Genetic diversity</topic><topic>Genotype</topic><topic>Heritability</topic><topic>Histocompatibility antigen HLA</topic><topic>HLA Antigens - genetics</topic><topic>Humanities and Social Sciences</topic><topic>Humans</topic><topic>Intelligence</topic><topic>Intelligence - genetics</topic><topic>Male</topic><topic>multidisciplinary</topic><topic>Multifactorial Inheritance</topic><topic>Polygenic inheritance</topic><topic>Polymorphism, Single Nucleotide</topic><topic>Science</topic><topic>Science (multidisciplinary)</topic><topic>Single-nucleotide polymorphism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zabaneh, Delilah</creatorcontrib><creatorcontrib>Krapohl, Eva</creatorcontrib><creatorcontrib>Simpson, Michael A.</creatorcontrib><creatorcontrib>Miller, Mike B.</creatorcontrib><creatorcontrib>Iacono, William G.</creatorcontrib><creatorcontrib>McGue, Matt</creatorcontrib><creatorcontrib>Putallaz, Martha</creatorcontrib><creatorcontrib>Lubinski, David</creatorcontrib><creatorcontrib>Plomin, Robert</creatorcontrib><creatorcontrib>Breen, Gerome</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>ProQuest Health and Medical</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</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>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</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 Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>ProQuest Science Journals</collection><collection>ProQuest Biological Science Journals</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 Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Scientific reports</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zabaneh, Delilah</au><au>Krapohl, Eva</au><au>Simpson, Michael A.</au><au>Miller, Mike B.</au><au>Iacono, William G.</au><au>McGue, Matt</au><au>Putallaz, Martha</au><au>Lubinski, David</au><au>Plomin, Robert</au><au>Breen, Gerome</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Fine mapping genetic associations between the HLA region and extremely high intelligence</atitle><jtitle>Scientific reports</jtitle><stitle>Sci Rep</stitle><addtitle>Sci Rep</addtitle><date>2017-01-24</date><risdate>2017</risdate><volume>7</volume><issue>1</issue><spage>41182</spage><epage>41182</epage><pages>41182-41182</pages><artnum>41182</artnum><issn>2045-2322</issn><eissn>2045-2322</eissn><abstract>General cognitive ability (intelligence) is one of the most heritable behavioural traits and most predictive of socially important outcomes and health. We hypothesized that some of the missing heritability of IQ might lie hidden in the human leukocyte antigen (HLA) region, which plays a critical role in many diseases and traits but is not well tagged in conventional GWAS. Using a uniquely powered design, we investigated whether fine-mapping of the HLA region could narrow the missing heritability gap. Our case-control design included 1,393 cases with extremely high intelligence scores (top 0.0003 of the population equivalent to IQ > 147) and 3,253 unselected population controls. We imputed variants in 200 genes across the HLA region, one SNP (rs444921) reached our criterion for study-wide significance. SNP-based heritability of the HLA variants was small and not significant (h
2
= 0.3%, SE = 0.2%). A polygenic score from the case-control genetic association analysis of SNPs in the HLA region did not significantly predict individual differences in intelligence in an independent unselected sample. We conclude that although genetic variation in the HLA region is important to the aetiology of many disorders, it does not appear to be hiding much of the missing heritability of intelligence.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>28117369</pmid><doi>10.1038/srep41182</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | 45 45/43 631/208/1515 631/208/205 Association analysis Case-Control Studies Chromosome Mapping - methods Cognitive ability Female Gene mapping Genetic diversity Genotype Heritability Histocompatibility antigen HLA HLA Antigens - genetics Humanities and Social Sciences Humans Intelligence Intelligence - genetics Male multidisciplinary Multifactorial Inheritance Polygenic inheritance Polymorphism, Single Nucleotide Science Science (multidisciplinary) Single-nucleotide polymorphism |
| title | Fine mapping genetic associations between the HLA region and extremely high intelligence |
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