Prioritization of Genetic Variants in the microRNA Regulome as Functional Candidates in Genome‐Wide Association Studies
Identifieur interne : 001585 ( Istex/Corpus ); précédent : 001584; suivant : 001586Prioritization of Genetic Variants in the microRNA Regulome as Functional Candidates in Genome‐Wide Association Studies
Auteurs : Brendan Bulik-Sullivan ; Sara Selitsky ; Praveen SethupathySource :
- Human Mutation [ 1059-7794 ] ; 2013-08.
Abstract
Comprehensive analyses of results from genome‐wide association studies (GWAS) have demonstrated that complex disease/trait‐associated loci are enriched in gene regulatory regions of the genome. The search for causal regulatory variation has focused primarily on transcriptional elements, such as promoters and enhancers. microRNAs (miRNAs) are now widely appreciated as critical posttranscriptional regulators of gene expression and are thought to impart stability to biological systems. Naturally occurring genetic variation in the miRNA regulome is likely an important contributor to phenotypic variation in the human population. However, the extent to which polymorphic miRNA‐mediated gene regulation underlies GWAS signals remains unclear. In this study, we have developed the most comprehensive bioinformatic analysis pipeline to date for cataloging and prioritizing variants in the miRNA regulome as functional candidates in GWAS. We highlight specific findings, including a variant in the promoter of the miRNA let‐7 that may contribute to human height variation. We also provide a discussion of how our approach can be expanded in the future. Overall, we believe that the results of this study will be valuable for researchers interested in determining whether GWAS signals implicate the miRNA regulome in their disease/trait of interest.
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DOI: 10.1002/humu.22337
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<record><TEI wicri:istexFullTextTei="biblStruct"><teiHeader><fileDesc><titleStmt><title xml:lang="en">Prioritization of Genetic Variants in the microRNA Regulome as Functional Candidates in Genome‐Wide Association Studies</title><author><name sortKey="Bulik Ullivan, Brendan" sort="Bulik Ullivan, Brendan" uniqKey="Bulik Ullivan B" first="Brendan" last="Bulik-Sullivan">Brendan Bulik-Sullivan</name><affiliation><mods:affiliation>Department of Genetics, University of North Carolina at Chapel Hill, North Carolina, Chapel Hill</mods:affiliation></affiliation></author><author><name sortKey="Selitsky, Sara" sort="Selitsky, Sara" uniqKey="Selitsky S" first="Sara" last="Selitsky">Sara Selitsky</name><affiliation><mods:affiliation>Department of Genetics, University of North Carolina at Chapel Hill, North Carolina, Chapel Hill</mods:affiliation></affiliation></author><author><name sortKey="Sethupathy, Praveen" sort="Sethupathy, Praveen" uniqKey="Sethupathy P" first="Praveen" last="Sethupathy">Praveen Sethupathy</name><affiliation><mods:affiliation>Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina</mods:affiliation></affiliation><affiliation><mods:affiliation>Carolina Center for Genome Sciences, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina</mods:affiliation></affiliation><affiliation><mods:affiliation>Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, North Carolina, Chapel Hill</mods:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">ISTEX</idno><idno type="RBID">ISTEX:C196A1ECAC012D9CFC916FBACBD0A7684989E442</idno><date when="2013" year="2013">2013</date><idno type="doi">10.1002/humu.22337</idno><idno type="url">https://api.istex.fr/document/C196A1ECAC012D9CFC916FBACBD0A7684989E442/fulltext/pdf</idno><idno type="wicri:Area/Istex/Corpus">001585</idno></publicationStmt><sourceDesc><biblStruct><analytic><title level="a" type="main" xml:lang="en">Prioritization of Genetic Variants in the microRNA Regulome as Functional Candidates in Genome‐Wide Association Studies</title><author><name sortKey="Bulik Ullivan, Brendan" sort="Bulik Ullivan, Brendan" uniqKey="Bulik Ullivan B" first="Brendan" last="Bulik-Sullivan">Brendan Bulik-Sullivan</name><affiliation><mods:affiliation>Department of Genetics, University of North Carolina at Chapel Hill, North Carolina, Chapel Hill</mods:affiliation></affiliation></author><author><name sortKey="Selitsky, Sara" sort="Selitsky, Sara" uniqKey="Selitsky S" first="Sara" last="Selitsky">Sara Selitsky</name><affiliation><mods:affiliation>Department of Genetics, University of North Carolina at Chapel Hill, North Carolina, Chapel Hill</mods:affiliation></affiliation></author><author><name sortKey="Sethupathy, Praveen" sort="Sethupathy, Praveen" uniqKey="Sethupathy P" first="Praveen" last="Sethupathy">Praveen Sethupathy</name><affiliation><mods:affiliation>Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina</mods:affiliation></affiliation><affiliation><mods:affiliation>Carolina Center for Genome Sciences, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina</mods:affiliation></affiliation><affiliation><mods:affiliation>Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, North Carolina, Chapel Hill</mods:affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j">Human Mutation</title><title level="j" type="abbrev">Human Mutation</title><idno type="ISSN">1059-7794</idno><idno type="eISSN">1098-1004</idno><imprint><publisher>Blackwell Publishing Ltd</publisher><date type="published" when="2013-08">2013-08</date><biblScope unit="volume">34</biblScope><biblScope unit="issue">8</biblScope><biblScope unit="page" from="1049">1049</biblScope><biblScope unit="page" to="1056">1056</biblScope></imprint><idno type="ISSN">1059-7794</idno></series><idno type="istex">C196A1ECAC012D9CFC916FBACBD0A7684989E442</idno><idno type="DOI">10.1002/humu.22337</idno><idno type="ArticleID">HUMU22337</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">1059-7794</idno></seriesStmt></fileDesc><profileDesc><textClass></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract">Comprehensive analyses of results from genome‐wide association studies (GWAS) have demonstrated that complex disease/trait‐associated loci are enriched in gene regulatory regions of the genome. The search for causal regulatory variation has focused primarily on transcriptional elements, such as promoters and enhancers. microRNAs (miRNAs) are now widely appreciated as critical posttranscriptional regulators of gene expression and are thought to impart stability to biological systems. Naturally occurring genetic variation in the miRNA regulome is likely an important contributor to phenotypic variation in the human population. However, the extent to which polymorphic miRNA‐mediated gene regulation underlies GWAS signals remains unclear. In this study, we have developed the most comprehensive bioinformatic analysis pipeline to date for cataloging and prioritizing variants in the miRNA regulome as functional candidates in GWAS. We highlight specific findings, including a variant in the promoter of the miRNA let‐7 that may contribute to human height variation. We also provide a discussion of how our approach can be expanded in the future. Overall, we believe that the results of this study will be valuable for researchers interested in determining whether GWAS signals implicate the miRNA regulome in their disease/trait of interest.</div></front></TEI><istex><corpusName>wiley</corpusName><author><json:item><name>Brendan Bulik‐Sullivan</name><affiliations><json:string>Department of Genetics, University of North Carolina at Chapel Hill, North Carolina, Chapel Hill</json:string></affiliations></json:item><json:item><name>Sara Selitsky</name><affiliations><json:string>Department of Genetics, University of North Carolina at Chapel Hill, North Carolina, Chapel Hill</json:string></affiliations></json:item><json:item><name>Praveen Sethupathy</name><affiliations><json:string>Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina</json:string><json:string>Carolina Center for Genome Sciences, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina</json:string><json:string>Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, North Carolina, Chapel Hill</json:string></affiliations></json:item></author><subject><json:item><lang><json:string>eng</json:string></lang><value>microRNA</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>GWAS</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>gene regulation</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>polymorphism</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>complex disease</value></json:item></subject><articleId><json:string>HUMU22337</json:string></articleId><language><json:string>eng</json:string></language><originalGenre><json:string>article</json:string></originalGenre><abstract>Naturally occurring genetic variation in the microRNA regulome is likely an important contributor to phenotypic variation in the human population. 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E‐mail:</p></note><affiliation>Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina</affiliation><affiliation>Carolina Center for Genome Sciences, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina</affiliation><affiliation>Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, North Carolina, Chapel Hill</affiliation></author></analytic><monogr><title level="j">Human Mutation</title><title level="j" type="abbrev">Human Mutation</title><idno type="pISSN">1059-7794</idno><idno type="eISSN">1098-1004</idno><idno type="DOI">10.1002/(ISSN)1098-1004</idno><imprint><publisher>Blackwell Publishing Ltd</publisher><date type="published" when="2013-08"></date><biblScope unit="volume">34</biblScope><biblScope unit="issue">8</biblScope><biblScope unit="page" from="1049">1049</biblScope><biblScope unit="page" to="1056">1056</biblScope></imprint></monogr><idno type="istex">C196A1ECAC012D9CFC916FBACBD0A7684989E442</idno><idno type="DOI">10.1002/humu.22337</idno><idno type="ArticleID">HUMU22337</idno></biblStruct></sourceDesc></fileDesc><profileDesc><creation><date>2013-04-29</date></creation><langUsage><language ident="en">en</language></langUsage><abstract><p>Comprehensive analyses of results from genome‐wide association studies (GWAS) have demonstrated that complex disease/trait‐associated loci are enriched in gene regulatory regions of the genome. The search for causal regulatory variation has focused primarily on transcriptional elements, such as promoters and enhancers. microRNAs (miRNAs) are now widely appreciated as critical posttranscriptional regulators of gene expression and are thought to impart stability to biological systems. Naturally occurring genetic variation in the miRNA regulome is likely an important contributor to phenotypic variation in the human population. However, the extent to which polymorphic miRNA‐mediated gene regulation underlies GWAS signals remains unclear. In this study, we have developed the most comprehensive bioinformatic analysis pipeline to date for cataloging and prioritizing variants in the miRNA regulome as functional candidates in GWAS. We highlight specific findings, including a variant in the promoter of the miRNA let‐7 that may contribute to human height variation. We also provide a discussion of how our approach can be expanded in the future. Overall, we believe that the results of this study will be valuable for researchers interested in determining whether GWAS signals implicate the miRNA regulome in their disease/trait of interest.</p></abstract><abstract xml:lang="en" style="graphical"><p>Naturally occurring genetic variation in the microRNA regulome is likely an important contributor to phenotypic variation in the human population. In this study, we have developed the most comprehensive bioinformatic analysis pipeline to date for cataloging and prioritizing variants in the microRNA regulome as functional candidates in genome‐wide association studies. 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E‐mail: <email>praveen_sethupathy@med.unc.edu</email></correspondenceTo><linkGroup><link type="toTypesetVersion" href="file:HUMU.HUMU22337.pdf"></link></linkGroup></publicationMeta><contentMeta><titleGroup><title type="main">Prioritization of Genetic Variants in the micro<fc>RNA</fc> Regulome as Functional Candidates in Genome‐Wide Association Studies</title></titleGroup><creators><creator xml:id="humu22337-cr-0001" creatorRole="author" affiliationRef="#humu22337-aff-0001"><personName><givenNames>Brendan</givenNames><familyName>Bulik‐Sullivan</familyName></personName></creator><creator xml:id="humu22337-cr-0002" creatorRole="author" affiliationRef="#humu22337-aff-0001"><personName><givenNames>Sara</givenNames><familyName>Selitsky</familyName></personName></creator><creator xml:id="humu22337-cr-0003" creatorRole="author" affiliationRef="#humu22337-aff-0001 #humu22337-aff-0002 #humu22337-aff-0003" corresponding="yes"><personName><givenNames>Praveen</givenNames><familyName>Sethupathy</familyName></personName></creator></creators><affiliationGroup><affiliation xml:id="humu22337-aff-0001"><orgDiv>Department of Genetics</orgDiv><orgName>University of North Carolina at Chapel Hill</orgName><address><city>Chapel Hill</city><countryPart>North Carolina</countryPart></address></affiliation><affiliation xml:id="humu22337-aff-0002"><orgDiv>Carolina Center for Genome Sciences</orgDiv><orgName>University of North Carolina at Chapel Hill</orgName><address><city>Chapel Hill</city><countryPart>North Carolina</countryPart></address></affiliation><affiliation xml:id="humu22337-aff-0003"><orgDiv>Lineberger Comprehensive Cancer Center</orgDiv><orgName>University of North Carolina at Chapel Hill</orgName><address><city>Chapel Hill</city><countryPart>North Carolina</countryPart></address></affiliation></affiliationGroup><keywordGroup type="author"><keyword xml:id="humu22337-kwd-0001">micro<fc>RNA</fc></keyword><keyword xml:id="humu22337-kwd-0002"><fc>GWAS</fc></keyword><keyword xml:id="humu22337-kwd-0003">gene regulation</keyword><keyword xml:id="humu22337-kwd-0004">polymorphism</keyword><keyword xml:id="humu22337-kwd-0005">complex disease</keyword></keywordGroup><fundingInfo><fundingAgency>NIDDK/NIH (DK091318‐02)</fundingAgency></fundingInfo><supportingInformation><p>Disclaimer: Supplementary materials have been peer‐reviewed but not copyedited.</p><supportingInfoItem><mediaResource alt="supplementary_material" rendition="webOriginal" href="urn-x:wiley:10597794:media:humu22337:humu22337-sup-0001-S1"></mediaResource><caption>Supporting Information</caption></supportingInfoItem><supportingInfoItem><mediaResource alt="supplementary_material" rendition="webOriginal" href="urn-x:wiley:10597794:media:humu22337:humu22337-sup-0002-S1"></mediaResource><caption>Supporting Information</caption></supportingInfoItem></supportingInformation><abstractGroup><abstract type="main"><title type="main">ABSTRACT</title><p>Comprehensive analyses of results from genome‐wide association studies (<fc>GWAS</fc>) have demonstrated that complex disease/trait‐associated loci are enriched in gene regulatory regions of the genome. The search for causal regulatory variation has focused primarily on transcriptional elements, such as promoters and enhancers. micro<fc>RNA</fc>s (mi<fc>RNA</fc>s) are now widely appreciated as critical posttranscriptional regulators of gene expression and are thought to impart stability to biological systems. Naturally occurring genetic variation in the mi<fc>RNA</fc> regulome is likely an important contributor to phenotypic variation in the human population. However, the extent to which polymorphic mi<fc>RNA</fc>‐mediated gene regulation underlies <fc>GWAS</fc> signals remains unclear. In this study, we have developed the most comprehensive bioinformatic analysis pipeline to date for cataloging and prioritizing variants in the mi<fc>RNA</fc> regulome as functional candidates in <fc>GWAS</fc>. We highlight specific findings, including a variant in the promoter of the mi<fc>RNA</fc> let‐7 that may contribute to human height variation. We also provide a discussion of how our approach can be expanded in the future. Overall, we believe that the results of this study will be valuable for researchers interested in determining whether <fc>GWAS</fc> signals implicate the mi<fc>RNA</fc> regulome in their disease/trait of interest.</p></abstract><abstract xml:id="humu22337-abs-0001" type="graphical" xml:lang="en"><p>Naturally occurring genetic variation in the microRNA regulome is likely an important contributor to phenotypic variation in the human population. In this study, we have developed the most comprehensive bioinformatic analysis pipeline to date for cataloging and prioritizing variants in the microRNA regulome as functional candidates in genome‐wide association studies. We highlight specific findings, including a variant in the promoter of the miRNA let‐7 that may contribute to human height variation. <blockFixed type="graphic"><mediaResourceGroup><mediaResource alt="image" href="urn:x-wiley:10597794:media:humu22337:humu22337-gra-0001"></mediaResource></mediaResourceGroup></blockFixed></p></abstract></abstractGroup></contentMeta><noteGroup><note xml:id="humu22337-note-0001" numbered="no"><p>Communicated by Arupa Ganguly</p></note><note xml:id="humu22337-note-0002" numbered="no"><p>[The copyright line for this article was changed on 9 June 2014 after original online publication.]</p></note></noteGroup></header></component></istex:document></istex:metadataXml><mods version="3.6"><titleInfo lang="en"><title>Prioritization of Genetic Variants in the microRNA Regulome as Functional Candidates in Genome‐Wide Association Studies</title></titleInfo><titleInfo type="alternative" contentType="CDATA" lang="en"><title>Prioritization of Genetic Variants in the microRNA Regulome as Functional Candidates in Genome‐Wide Association Studies</title></titleInfo><name type="personal"><namePart type="given">Brendan</namePart><namePart type="family">Bulik‐Sullivan</namePart><affiliation>Department of Genetics, University of North Carolina at Chapel Hill, North Carolina, Chapel Hill</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Sara</namePart><namePart type="family">Selitsky</namePart><affiliation>Department of Genetics, University of North Carolina at Chapel Hill, North Carolina, Chapel Hill</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Praveen</namePart><namePart type="family">Sethupathy</namePart><affiliation>Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina</affiliation><affiliation>Carolina Center for Genome Sciences, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina</affiliation><affiliation>Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, North Carolina, Chapel Hill</affiliation><description>Correspondence to: Praveen Sethupathy, Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599. E‐mail: </description><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="article" displayLabel="article"></genre><originInfo><publisher>Blackwell Publishing Ltd</publisher><dateIssued encoding="w3cdtf">2013-08</dateIssued><dateCreated encoding="w3cdtf">2013-04-29</dateCreated><dateCaptured encoding="w3cdtf">2013-01-15</dateCaptured><dateValid encoding="w3cdtf">2013-04-03</dateValid><copyrightDate encoding="w3cdtf">2013</copyrightDate></originInfo><language><languageTerm type="code" authority="rfc3066">en</languageTerm><languageTerm type="code" authority="iso639-2b">eng</languageTerm></language><physicalDescription><internetMediaType>text/html</internetMediaType></physicalDescription><abstract>Comprehensive analyses of results from genome‐wide association studies (GWAS) have demonstrated that complex disease/trait‐associated loci are enriched in gene regulatory regions of the genome. The search for causal regulatory variation has focused primarily on transcriptional elements, such as promoters and enhancers. microRNAs (miRNAs) are now widely appreciated as critical posttranscriptional regulators of gene expression and are thought to impart stability to biological systems. Naturally occurring genetic variation in the miRNA regulome is likely an important contributor to phenotypic variation in the human population. However, the extent to which polymorphic miRNA‐mediated gene regulation underlies GWAS signals remains unclear. In this study, we have developed the most comprehensive bioinformatic analysis pipeline to date for cataloging and prioritizing variants in the miRNA regulome as functional candidates in GWAS. We highlight specific findings, including a variant in the promoter of the miRNA let‐7 that may contribute to human height variation. We also provide a discussion of how our approach can be expanded in the future. Overall, we believe that the results of this study will be valuable for researchers interested in determining whether GWAS signals implicate the miRNA regulome in their disease/trait of interest.</abstract><abstract type="graphical" lang="en">Naturally occurring genetic variation in the microRNA regulome is likely an important contributor to phenotypic variation in the human population. In this study, we have developed the most comprehensive bioinformatic analysis pipeline to date for cataloging and prioritizing variants in the microRNA regulome as functional candidates in genome‐wide association studies. We highlight specific findings, including a variant in the promoter of the miRNA let‐7 that may contribute to human height variation.</abstract><note type="funding">NIDDK/NIH (DK091318‐02)</note><subject><genre>keywords</genre><topic>microRNA</topic><topic>GWAS</topic><topic>gene regulation</topic><topic>polymorphism</topic><topic>complex disease</topic></subject><relatedItem type="host"><titleInfo><title>Human Mutation</title></titleInfo><titleInfo type="abbreviated"><title>Human Mutation</title></titleInfo><genre type="journal">journal</genre><note type="content"> Disclaimer: Supplementary materials have been peer‐reviewed but not copyedited.Supporting Info Item: Supporting Information - Supporting Information - </note><subject><genre>article-category</genre><topic>Informatic</topic></subject><identifier type="ISSN">1059-7794</identifier><identifier type="eISSN">1098-1004</identifier><identifier type="DOI">10.1002/(ISSN)1098-1004</identifier><identifier type="PublisherID">HUMU</identifier><part><date>2013</date><detail type="volume"><caption>vol.</caption><number>34</number></detail><detail type="issue"><caption>no.</caption><number>8</number></detail><extent unit="pages"><start>1049</start><end>1056</end><total>8</total></extent></part></relatedItem><identifier type="istex">C196A1ECAC012D9CFC916FBACBD0A7684989E442</identifier><identifier type="DOI">10.1002/humu.22337</identifier><identifier type="ArticleID">HUMU22337</identifier><accessCondition type="use and reproduction" contentType="creativeCommonsBy-nc">This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.</accessCondition><recordInfo><recordContentSource>WILEY</recordContentSource></recordInfo></mods></metadata><enrichments><json:item><type>multicat</type><uri>https://api.istex.fr/document/C196A1ECAC012D9CFC916FBACBD0A7684989E442/enrichments/multicat</uri></json:item></enrichments><serie></serie></istex></record>Pour manipuler ce document sous Unix (Dilib)
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