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Candidate gene studies of ADHD: a meta-analytic review | Human Genetics

<!DOCTYPE html> <html lang="en" class="no-js"> <head> <meta charset="UTF-8"> <meta http-equiv="X-UA-Compatible" content="IE=edge"> <meta name="applicable-device" content="pc,mobile"> <meta name="viewport" content="width=device-width, initial-scale=1"> <meta name="robots" content="max-image-preview:large"> <meta name="access" content="No"> <meta name="360-site-verification" content="1268d79b5e96aecf3ff2a7dac04ad990" /> <title>Candidate gene studies of ADHD: a meta-analytic review | Human Genetics</title> <meta name="twitter:site" content="@SpringerLink"/> <meta name="twitter:card" content="summary_large_image"/> <meta name="twitter:image:alt" content="Content cover image"/> <meta name="twitter:title" content="Candidate gene studies of ADHD: a meta-analytic review"/> <meta name="twitter:description" content="Human Genetics - Quantitative genetic studies (i.e., twin and adoption studies) suggest that genetic influences contribute substantially to the development of attention deficit hyperactivity..."/> <meta name="twitter:image" content="https://static-content.springer.com/image/art%3A10.1007%2Fs00439-009-0694-x/MediaObjects/439_2009_694_Fig1_HTML.gif"/> <meta name="journal_id" content="439"/> <meta name="dc.title" content="Candidate gene studies of ADHD: a meta-analytic review"/> <meta name="dc.source" content="Human Genetics 2009 126:1"/> <meta name="dc.format" content="text/html"/> <meta name="dc.publisher" content="Springer"/> <meta name="dc.date" content="2009-06-09"/> <meta name="dc.type" content="ReviewPaper"/> <meta name="dc.language" content="En"/> <meta name="dc.copyright" content="2009 Springer-Verlag"/> <meta name="dc.rights" content="2009 Springer-Verlag"/> <meta name="dc.rightsAgent" content="journalpermissions@springernature.com"/> <meta name="dc.description" content="Quantitative genetic studies (i.e., twin and adoption studies) suggest that genetic influences contribute substantially to the development of attention deficit hyperactivity disorder (ADHD). Over the past 15&amp;nbsp;years, considerable efforts have been made to identify genes involved in the etiology of this disorder resulting in a large and often conflicting literature of candidate gene associations for ADHD. The first aim of the present study was to conduct a comprehensive meta-analytic review of this literature to determine which candidate genes show consistent evidence of association with childhood ADHD across studies. The second aim was to test for heterogeneity across studies in the effect sizes for each candidate gene as its presence might suggest moderating variables that could explain inconsistent results. Significant associations were identified for several candidate genes including DAT1, DRD4, DRD5, 5HTT, HTR1B, and SNAP25. Further, significant heterogeneity was observed for the associations between ADHD and DAT1, DRD4, DRD5, DBH, ADRA2A, 5HTT, TPH2, MAOA, and SNAP25, suggesting that future studies should explore potential moderators of these associations (e.g., ADHD subtype diagnoses, gender, exposure to environmental risk factors). We conclude with a discussion of these findings in relation to emerging themes relevant to future studies of the genetics of ADHD."/> <meta name="prism.issn" content="1432-1203"/> <meta name="prism.publicationName" content="Human Genetics"/> <meta name="prism.publicationDate" content="2009-06-09"/> <meta name="prism.volume" content="126"/> <meta name="prism.number" content="1"/> <meta name="prism.section" content="ReviewPaper"/> <meta name="prism.startingPage" content="51"/> <meta name="prism.endingPage" content="90"/> <meta name="prism.copyright" content="2009 Springer-Verlag"/> <meta name="prism.rightsAgent" content="journalpermissions@springernature.com"/> <meta name="prism.url" content="https://link.springer.com/article/10.1007/s00439-009-0694-x"/> <meta name="prism.doi" content="doi:10.1007/s00439-009-0694-x"/> <meta name="citation_pdf_url" content="https://link.springer.com/content/pdf/10.1007/s00439-009-0694-x.pdf"/> <meta name="citation_fulltext_html_url" content="https://link.springer.com/article/10.1007/s00439-009-0694-x"/> <meta name="citation_journal_title" content="Human Genetics"/> <meta name="citation_journal_abbrev" content="Hum Genet"/> <meta name="citation_publisher" content="Springer-Verlag"/> <meta name="citation_issn" content="1432-1203"/> <meta name="citation_title" content="Candidate gene studies of ADHD: a meta-analytic review"/> <meta name="citation_volume" content="126"/> <meta name="citation_issue" content="1"/> <meta name="citation_publication_date" content="2009/07"/> <meta name="citation_online_date" content="2009/06/09"/> <meta name="citation_firstpage" content="51"/> <meta name="citation_lastpage" content="90"/> <meta name="citation_article_type" content="Review Article"/> <meta name="citation_language" content="en"/> <meta name="dc.identifier" content="doi:10.1007/s00439-009-0694-x"/> <meta name="DOI" content="10.1007/s00439-009-0694-x"/> <meta name="size" content="1088092"/> <meta name="citation_doi" content="10.1007/s00439-009-0694-x"/> <meta name="citation_springer_api_url" content="http://api.springer.com/xmldata/jats?q=doi:10.1007/s00439-009-0694-x&amp;api_key="/> <meta name="description" content="Quantitative genetic studies (i.e., twin and adoption studies) suggest that genetic influences contribute substantially to the development of attention def"/> <meta name="dc.creator" content="Gizer, Ian R."/> <meta name="dc.creator" content="Ficks, Courtney"/> <meta name="dc.creator" content="Waldman, Irwin D."/> <meta name="dc.subject" content="Human Genetics"/> <meta name="dc.subject" content="Molecular Medicine"/> <meta name="dc.subject" content="Gene Function"/> <meta name="dc.subject" content="Metabolic Diseases"/> <meta name="citation_reference" content="citation_journal_title=J Consult Clin Psychol; citation_title=The child behavior profile: II. 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Clinical efficacy; citation_author=A Zametkin, JL Rapoport, DL Murphy, M Linnoila, D Ismond; citation_volume=42; citation_publication_date=1985; citation_pages=962-966; citation_id=CR343"/> <meta name="citation_reference" content="citation_journal_title=Zhonghua yi xue yi chuan xue za zhi; citation_title=Association analysis between attention-deficit hyperactivity disorder and Val158Met polymorphism of catechol-O-methyltransferase gene; citation_author=XN Zhang, LM Ruan, YP Le, Y Zhang; citation_volume=20; citation_publication_date=2003; citation_pages=322-324; citation_id=CR344"/> <meta name="citation_reference" content="citation_journal_title=Int J Neurosci; citation_title=Association analysis of serotonin transporter promoter gene polymorphism with ADHD and related symptomatology; citation_author=AL Zhao, LY Su, YH Zhang, BS Tang, XR Luo, CX Huang, QR Su; citation_volume=115; citation_publication_date=2005; citation_pages=1183-1191; citation_doi=10.1080/00207450590914545; citation_id=CR345"/> <meta name="citation_reference" content="citation_journal_title=Neuropsychobiology; citation_title=Significance of serotonin transporter gene 5-HTTLPR and variable number of tandem repeat polymorphism in attention deficit hyperactivity disorder; citation_author=SS Zoroglu, ME Erdal, B Alasehirli, N Erdal, H Tutkun, HA Savas, H Herken; citation_volume=45; citation_publication_date=2002; citation_pages=176-181; citation_doi=10.1159/000063667; citation_id=CR346"/> <meta name="citation_reference" content="citation_journal_title=Neuropsychobiology; citation_title=No evidence for an association between the T102C and 1438 G/A polymorphisms of the serotonin receptor gene in attention deficit/hyperactivity disorder in a Tukish population; citation_author=SS Zoroglu, ME Erdal, N Erdal, S Ozen, B Alasehirli, E Sivasli; citation_volume=47; citation_publication_date=2003; citation_pages=17-20; citation_doi=10.1159/000068870; citation_id=CR347"/> <meta name="citation_author" content="Gizer, Ian R."/> <meta name="citation_author_email" content="igizer@unc.edu"/> <meta name="citation_author_institution" content="Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, USA"/> <meta name="citation_author" content="Ficks, Courtney"/> <meta name="citation_author_email" content="courtney.ficks@emory.edu"/> <meta name="citation_author_institution" content="Department of Psychology, Emory University, Atlanta, USA"/> <meta name="citation_author" content="Waldman, Irwin D."/> <meta name="citation_author_email" content="psyiw@emory.edu"/> <meta name="citation_author_institution" content="Department of Psychology, Emory University, Atlanta, USA"/> <meta name="format-detection" content="telephone=no"/> <meta name="citation_cover_date" content="2009/07/01"/> <meta property="og:url" content="https://link.springer.com/article/10.1007/s00439-009-0694-x"/> <meta property="og:type" content="article"/> <meta property="og:site_name" content="SpringerLink"/> <meta property="og:title" content="Candidate gene studies of ADHD: a meta-analytic review - Human Genetics"/> <meta property="og:description" content="Quantitative genetic studies (i.e., twin and adoption studies) suggest that genetic influences contribute substantially to the development of attention deficit hyperactivity disorder (ADHD). Over the past 15 years, considerable efforts have been made to identify genes involved in the etiology of this disorder resulting in a large and often conflicting literature of candidate gene associations for ADHD. The first aim of the present study was to conduct a comprehensive meta-analytic review of this literature to determine which candidate genes show consistent evidence of association with childhood ADHD across studies. The second aim was to test for heterogeneity across studies in the effect sizes for each candidate gene as its presence might suggest moderating variables that could explain inconsistent results. Significant associations were identified for several candidate genes including DAT1, DRD4, DRD5, 5HTT, HTR1B, and SNAP25. Further, significant heterogeneity was observed for the associations between ADHD and DAT1, DRD4, DRD5, DBH, ADRA2A, 5HTT, TPH2, MAOA, and SNAP25, suggesting that future studies should explore potential moderators of these associations (e.g., ADHD subtype diagnoses, gender, exposure to environmental risk factors). We conclude with a discussion of these findings in relation to emerging themes relevant to future studies of the genetics of ADHD."/> <meta property="og:image" content="https://static-content.springer.com/image/art%3A10.1007%2Fs00439-009-0694-x/MediaObjects/439_2009_694_Fig1_HTML.gif"/> <meta name="format-detection" content="telephone=no"> <link rel="apple-touch-icon" sizes="180x180" href=/oscar-static/img/favicons/darwin/apple-touch-icon-92e819bf8a.png> <link rel="icon" type="image/png" sizes="192x192" href=/oscar-static/img/favicons/darwin/android-chrome-192x192-6f081ca7e5.png> <link rel="icon" type="image/png" sizes="32x32" href=/oscar-static/img/favicons/darwin/favicon-32x32-1435da3e82.png> <link rel="icon" type="image/png" sizes="16x16" href=/oscar-static/img/favicons/darwin/favicon-16x16-ed57f42bd2.png> <link rel="shortcut icon" data-test="shortcut-icon" href=/oscar-static/img/favicons/darwin/favicon-c6d59aafac.ico> <meta name="theme-color" content="#e6e6e6"> <!-- Please see 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class="app-article-masthead__journal-title">Human Genetics</span> </a> <a href="https://link.springer.com/journal/439/aims-and-scope" class="app-article-masthead__submission-link" data-track="click_aims_and_scope" data-track-action="aims and scope" data-track-context="article page" data-track-label="link"> Aims and scope <svg width="16" height="16" focusable="false" role="img" aria-hidden="true" class="u-icon"><use xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="#icon-eds-i-arrow-right-medium"></use></svg> </a> <a href="https://submission.springernature.com/new-submission/439/3" class="app-article-masthead__submission-link" data-track="click_submit_manuscript" data-track-context="article masthead on springerlink article page" data-track-action="submit manuscript" data-track-label="link"> Submit manuscript <svg width="16" height="16" focusable="false" role="img" aria-hidden="true" class="u-icon"><use xmlns:xlink="http://www.w3.org/1999/xlink" 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Gizer<svg width="16" height="16" focusable="false" role="img" aria-hidden="true" class="u-icon"><use xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="#icon-eds-i-mail-medium"></use></svg></a><sup class="u-js-hide"><a href="#Aff1">1</a></sup>, </li><li class="c-article-author-list__item"><a data-test="author-name" data-track="click" data-track-action="open author" data-track-label="link" href="#auth-Courtney-Ficks-Aff2" data-author-popup="auth-Courtney-Ficks-Aff2" data-author-search="Ficks, Courtney">Courtney Ficks</a><sup class="u-js-hide"><a href="#Aff2">2</a></sup> &amp; </li><li class="c-article-author-list__item"><a data-test="author-name" data-track="click" data-track-action="open author" data-track-label="link" href="#auth-Irwin_D_-Waldman-Aff2" data-author-popup="auth-Irwin_D_-Waldman-Aff2" data-author-search="Waldman, Irwin D.">Irwin D. Waldman</a><sup class="u-js-hide"><a href="#Aff2">2</a></sup> </li></ul> <div data-test="article-metrics"> <ul class="app-article-metrics-bar u-list-reset"> <li class="app-article-metrics-bar__item"> <p class="app-article-metrics-bar__count"><svg class="u-icon app-article-metrics-bar__icon" width="24" height="24" aria-hidden="true" focusable="false"> <use xlink:href="#icon-eds-i-accesses-medium"></use> </svg>12k <span class="app-article-metrics-bar__label">Accesses</span></p> </li> <li class="app-article-metrics-bar__item"> <p class="app-article-metrics-bar__count"><svg class="u-icon app-article-metrics-bar__icon" width="24" height="24" aria-hidden="true" focusable="false"> <use xlink:href="#icon-eds-i-citations-medium"></use> </svg>751 <span class="app-article-metrics-bar__label">Citations</span></p> </li> <li class="app-article-metrics-bar__item"> <p class="app-article-metrics-bar__count"><svg class="u-icon app-article-metrics-bar__icon" width="24" height="24" aria-hidden="true" focusable="false"> <use xlink:href="#icon-eds-i-altmetric-medium"></use> </svg>30 <span class="app-article-metrics-bar__label">Altmetric</span></p> </li> <li class="app-article-metrics-bar__item"> <p class="app-article-metrics-bar__count"><svg class="u-icon app-article-metrics-bar__icon app-article-metrics-bar__icon--mentions" width="24" height="24" aria-hidden="true" focusable="false"> <use xlink:href="#icon-eds-i-mentions-medium"></use> </svg>1 <span class="app-article-metrics-bar__label">Mention</span></p> </li> <li class="app-article-metrics-bar__item app-article-metrics-bar__item--metrics"> <p class="app-article-metrics-bar__details"><a href="/article/10.1007/s00439-009-0694-x/metrics" data-track="click" data-track-action="view metrics" data-track-label="link" rel="nofollow">Explore all metrics <svg class="u-icon app-article-metrics-bar__arrow-icon" width="24" height="24" aria-hidden="true" focusable="false"> <use xlink:href="#icon-eds-i-arrow-right-medium"></use> </svg></a></p> </li> </ul> </div> <div class="u-mt-32"> </div> </header> </div> <div data-article-body="true" data-track-component="article body" class="c-article-body"> <section aria-labelledby="Abs1" data-title="Abstract" lang="en"><div class="c-article-section" id="Abs1-section"><h2 class="c-article-section__title js-section-title js-c-reading-companion-sections-item" id="Abs1">Abstract</h2><div class="c-article-section__content" id="Abs1-content"><p>Quantitative genetic studies (i.e., twin and adoption studies) suggest that genetic influences contribute substantially to the development of attention deficit hyperactivity disorder (ADHD). Over the past 15 years, considerable efforts have been made to identify genes involved in the etiology of this disorder resulting in a large and often conflicting literature of candidate gene associations for ADHD. The first aim of the present study was to conduct a comprehensive meta-analytic review of this literature to determine which candidate genes show consistent evidence of association with childhood ADHD across studies. The second aim was to test for heterogeneity across studies in the effect sizes for each candidate gene as its presence might suggest moderating variables that could explain inconsistent results. Significant associations were identified for several candidate genes including <i>DAT1, DRD4, DRD5, 5HTT, HTR1B,</i> and <i>SNAP25.</i> Further, significant heterogeneity was observed for the associations between ADHD and <i>DAT1, DRD4, DRD5, DBH, ADRA2A, 5HTT, TPH2, MAOA,</i> and <i>SNAP25,</i> suggesting that future studies should explore potential moderators of these associations (e.g., ADHD subtype diagnoses, gender, exposure to environmental risk factors). 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js-c-reading-companion-figures-item" data-test="figure" data-container-section="figure" id="figure-18"><figure><figcaption><b id="Fig18" class="c-article-section__figure-caption" data-test="figure-caption-text">Fig. 18</b></figcaption><div class="c-article-section__figure-content"><div class="c-article-section__figure-item"><picture><source type="image/webp" srcset="//media.springernature.com/m312/springer-static/image/art%3A10.1007%2Fs00439-009-0694-x/MediaObjects/439_2009_694_Fig18_HTML.gif?as=webp"><img src="//media.springernature.com/m312/springer-static/image/art%3A10.1007%2Fs00439-009-0694-x/MediaObjects/439_2009_694_Fig18_HTML.gif" alt="" loading="lazy"></picture></div></div></figure></div><div class="c-article-section__figure js-c-reading-companion-figures-item" data-test="figure" data-container-section="figure" id="figure-19"><figure><figcaption><b id="Fig19" class="c-article-section__figure-caption" data-test="figure-caption-text">Fig. 19</b></figcaption><div class="c-article-section__figure-content"><div class="c-article-section__figure-item"><picture><source type="image/webp" srcset="//media.springernature.com/m312/springer-static/image/art%3A10.1007%2Fs00439-009-0694-x/MediaObjects/439_2009_694_Fig19_HTML.gif?as=webp"><img src="//media.springernature.com/m312/springer-static/image/art%3A10.1007%2Fs00439-009-0694-x/MediaObjects/439_2009_694_Fig19_HTML.gif" alt="" loading="lazy"></picture></div></div></figure></div><div class="c-article-section__figure js-c-reading-companion-figures-item" data-test="figure" data-container-section="figure" id="figure-20"><figure><figcaption><b id="Fig20" class="c-article-section__figure-caption" data-test="figure-caption-text">Fig. 20</b></figcaption><div class="c-article-section__figure-content"><div class="c-article-section__figure-item"><picture><source type="image/webp" srcset="//media.springernature.com/m312/springer-static/image/art%3A10.1007%2Fs00439-009-0694-x/MediaObjects/439_2009_694_Fig20_HTML.gif?as=webp"><img src="//media.springernature.com/m312/springer-static/image/art%3A10.1007%2Fs00439-009-0694-x/MediaObjects/439_2009_694_Fig20_HTML.gif" alt="" loading="lazy"></picture></div></div></figure></div><div class="c-article-section__figure js-c-reading-companion-figures-item" data-test="figure" data-container-section="figure" id="figure-21"><figure><figcaption><b id="Fig21" class="c-article-section__figure-caption" data-test="figure-caption-text">Fig. 21</b></figcaption><div class="c-article-section__figure-content"><div class="c-article-section__figure-item"><picture><source type="image/webp" srcset="//media.springernature.com/m312/springer-static/image/art%3A10.1007%2Fs00439-009-0694-x/MediaObjects/439_2009_694_Fig21_HTML.gif?as=webp"><img 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Preparation of this article was supported in part by a grant from the National Institutes of Health to IRG (T32 AA007573; PI Dr. Fulton Crews).</p></div></div></section><section aria-labelledby="author-information" data-title="Author information"><div class="c-article-section" id="author-information-section"><h2 class="c-article-section__title js-section-title js-c-reading-companion-sections-item" id="author-information">Author information</h2><div class="c-article-section__content" id="author-information-content"><h3 class="c-article__sub-heading" id="affiliations">Authors and Affiliations</h3><ol class="c-article-author-affiliation__list"><li id="Aff1"><p class="c-article-author-affiliation__address">Department of Genetics, University of North Carolina at Chapel Hill, 120 Mason Farm Road, Room 5015 Genetic Medicine Building CB 7264, Chapel Hill, NC, 27599-7264, USA</p><p class="c-article-author-affiliation__authors-list">Ian R. Gizer</p></li><li id="Aff2"><p class="c-article-author-affiliation__address">Department of Psychology, Emory University, Atlanta, GA, USA</p><p class="c-article-author-affiliation__authors-list">Courtney Ficks &amp; Irwin D. Waldman</p></li></ol><div class="u-js-hide u-hide-print" data-test="author-info"><span class="c-article__sub-heading">Authors</span><ol class="c-article-authors-search u-list-reset"><li id="auth-Ian_R_-Gizer-Aff1"><span class="c-article-authors-search__title u-h3 js-search-name">Ian R. 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Candidate gene studies of ADHD: a meta-analytic review. <i>Hum Genet</i> <b>126</b>, 51–90 (2009). https://doi.org/10.1007/s00439-009-0694-x</p><p class="c-bibliographic-information__download-citation u-hide-print"><a data-test="citation-link" data-track="click" data-track-action="download article citation" data-track-label="link" data-track-external="" rel="nofollow" href="https://citation-needed.springer.com/v2/references/10.1007/s00439-009-0694-x?format=refman&amp;flavour=citation">Download citation<svg width="16" height="16" focusable="false" role="img" aria-hidden="true" class="u-icon"><use xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="#icon-eds-i-download-medium"></use></svg></a></p><ul class="c-bibliographic-information__list" data-test="publication-history"><li class="c-bibliographic-information__list-item"><p>Received<span class="u-hide">: </span><span class="c-bibliographic-information__value"><time datetime="2009-05-20">20 May 2009</time></span></p></li><li 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