The Gene Expression Landscape of Disease Genes

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usa-input-error-message selection-validation-message"> Name must be less than 100 characters </div> </div> <div class="action-panel-control-wrap existing-collections-controls"> <label for="collections-action-panel-add-to-existing" class="action-panel-label"> Choose a collection: </label> <select id="collections-action-panel-add-to-existing" class="action-panel-selector collections-action-add-to-existing" data-ga-category="save_share" data-ga-action="select_collection" data-ga-label="($('#collections-action-add-to-existing').val() === 'Favorites') ? 'Favorites' : 'non_favorites_collection'"> </select> <div class="collections-retry-load-on-error usa-input-error-message selection-validation-message"> Unable to load your collection due to an error<br> <a href="#">Please try again</a> </div> </div> </div> <div class="action-panel-actions"> <button class="action-panel-submit" type="submit" data-loading-label="Adding..." data-pinger-ignore data-ga-category="save_share" data-ga-action="collections" data-ga-label="add"> Add </button> <button class="action-panel-cancel" aria-label="Close 'Add to Collections' panel" ref="linksrc=close_collections_panel" aria-controls="collections-action-panel" aria-expanded="false" data-ga-category="save_share" data-ga-action="collections" data-ga-label="cancel"> Cancel </button> </div> </form> </div> </div> <div id="bibliography-action-panel" class="bibliography-action-panel action-panel in-progress-dots-panel" aria-hidden="true" data-bibliography-open-panel-enabled="false" data-bibliography-open-panel-url-hash="#open-bibliography-panel"> <div class="inner-wrap"> <h3 class="action-panel-heading"> Add to My Bibliography </h3> <form id="bibliography-action-panel-form" class="bibliography-action-panel-form action-panel-content action-form action-panel-smaller-selectors" data-add-to-bibliography-max-amount="100" data-add-to-bibliography-batch-size="10" data-bibliography-delegates-url="/list-bibliography-delegates/" data-add-to-bibliography-url="/add-to-bibliography/" data-get-article-ids-by-search-url="/get-article-ids-by-search/" data-mybib-root-url="https://www.ncbi.nlm.nih.gov/myncbi/collections/mybibliography/"> <input type="hidden" name="csrfmiddlewaretoken" value="ecMLtYN8KWEyriFoSVIDayPIngWWftZaKdLdIsLYDl2JUf1iQZp2mTWsQ7jgLIIp"> <div class="action-panel-control-wrap bibliographies-controls"> <div class="choice-group"> <ul class="bibliographies-action-add radio-group-items"> <li> <input name="bibliography" id="my-bibliography" class="my-bibliography" type="radio" checked/> <label for="my-bibliography">My Bibliography</label> </li> </ul> </div> </div> <div class="bibliographies-retry-load-on-error usa-input-error-message selection-validation-message"> Unable to load your delegates due to an error<br> <a href="#">Please try again</a> </div> <div class="action-panel-actions"> <button class="action-panel-submit" type="submit" data-loading-label="Adding..." data-pinger-ignore> Add </button> <button class="action-panel-cancel" aria-label="Close 'Add to bibliography' panel" ref="linksrc=close_bibliography_panel" aria-controls="bibliography-action-panel" aria-expanded="false" data-ga-category="save_share" data-ga-action="mybib" data-ga-label="cancel"> Cancel </button> </div> </form> </div> </div> <div id="saved-search-action-panel" class="saved-search-action-panel action-panel " aria-hidden="true" data-saved-search-open-panel-enabled="false" data-saved-search-open-panel-url-hash="#open-saved-search-panel"> <div class="inner-wrap"> <h2 class="action-panel-heading"> Your saved search </h2> <form id="saved-search-action-panel-form" class="saved-search-action-panel-form action-panel-content action-form" data-create-saved-search-url="/create-saved-search/" data-try-search-terms-url="/try-search-term/" data-saved-search-root-url="https://www.ncbi.nlm.nih.gov/myncbi/searches/"> <input type="hidden" name="csrfmiddlewaretoken" value="ecMLtYN8KWEyriFoSVIDayPIngWWftZaKdLdIsLYDl2JUf1iQZp2mTWsQ7jgLIIp"> <div class="action-panel-control-wrap"> <label for="saved-search-name" class="action-panel-label saved-search-name-label required-field-asterisk"> Name of saved search: </label> <input maxlength="200" type="text" name="saved-search-name" id="saved-search-name" class="saved-search-name" value="" required pattern="[^"&=<>\/]*" title="The following characters are not allowed in the Name field: "&=<>/"> </div> <div class="action-panel-control-wrap"> <label for="saved-search-term" class="action-panel-label required-field-asterisk"> Search terms: </label> <textarea name="saved-search-term" id="saved-search-term" class="saved-search-term" required></textarea> </div> <div class="test-search-term-wrap"> <a href="#" class="try-search-term">Test search terms</a> </div> <div class="choice-group action-panel-extra-margin-top"> <span class="action-panel-label" id="fieldset-label"> Would you like email updates of new search results? </span> <fieldset id="saved-search-alert" aria-describedby="fieldset-label"> <legend class="usa-sr-only">Saved Search Alert Radio Buttons</legend> <ul class="radio-group-items"> <li> <input type="radio" id="saved-search-alert-yes" class="saved-search-alert-yes" name="saved-search-alert" value="yes" checked> <label for="saved-search-alert-yes" class="action-panel-label">Yes</label> </li> <li> <input aria-label="No radio input" type="radio" id="saved-search-alert-no" class="saved-search-alert-no" name="saved-search-alert" value="no"> <label for="saved-search-alert-no" class="action-panel-label">No</label> </li> </ul> </fieldset> </div> <div class="alert-schedule-wrap"> <div class="action-panel-control-wrap"> <label class="action-panel-label"> Email: </label> <span aria-label="Email address" id="saved-search-email" class="action-panel-label"><span class="action-panel-label-bold"></span> (<a class="myncbi-account-settings" href="https://www.ncbi.nlm.nih.gov/account/settings/">change</a>)</span> </div> <div class="action-panel-control-wrap action-panel-extra-margin-top"> <label for="saved-search-frequency" class="action-panel-label"> Frequency: </label> <select id="saved-search-frequency" class="no-border-panel-selector saved-search-frequency"> <option value="monthly">Monthly</option> <option value="weekly">Weekly</option> <option value="daily">Daily</option> </select> </div> <div class="action-panel-control-wrap saved-search-monthly-additional"> <label for="saved-search-monthly-on-day" class="action-panel-label"> Which day? </label> <select id="saved-search-monthly-on-day" class="no-border-panel-selector"> <option value="Sunday">The first Sunday</option> <option value="Monday">The first Monday</option> <option value="Tuesday">The first Tuesday</option> <option value="Wednesday">The first Wednesday</option> <option value="Thursday">The first Thursday</option> <option value="Friday">The first Friday</option> <option value="Saturday">The first Saturday</option> <option value="day">The first day</option> <option value="weekday">The first weekday</option> </select> </div> <div class="action-panel-control-wrap saved-search-weekly-additional"> <label for="saved-search-weekly-on-day" class="action-panel-label"> Which day? </label> <select id="saved-search-weekly-on-day" class="no-border-panel-selector saved-search-weekly-on-day"> <option value="Sunday">Sunday</option> <option value="Monday">Monday</option> <option value="Tuesday">Tuesday</option> <option value="Wednesday">Wednesday</option> <option value="Thursday">Thursday</option> <option value="Friday">Friday</option> <option value="Saturday">Saturday</option> </select> </div> <div class="action-panel-control-wrap"> <label for="saved-search-report" class="action-panel-label"> Report format: </label> <select id="saved-search-report" class="no-border-panel-selector saved-search-report"> <option value="DocSum">Summary</option> <option value="DocSumText">Summary (text)</option> <option value="Abstract">Abstract</option> <option value="AbstractText">Abstract (text)</option> <option value="MEDLINE">PubMed</option> </select> </div> <div class="action-panel-control-wrap"> <label for="saved-search-amount" class="action-panel-label"> Send at most: </label> <select id="saved-search-amount" class="no-border-panel-selector saved-search-amount"> <option value="1">1 item</option> <option value="5" selected>5 items</option> <option value="10">10 items</option> <option value="20">20 items</option> <option value="50">50 items</option> <option value="100">100 items</option> <option value="200">200 items</option> </select> </div> <div> <input type="checkbox" id="saved-search-send-if-no-result" class="saved-search-send-if-no-result" name="saved-search-send-if-no-result"> <label for="saved-search-send-if-no-result" class="action-panel-label smaller-checkbox"> Send even when there aren't any new results </label> </div> <div class="action-panel-control-wrap option-text-in-email-wrap"> <label for="saved-search-email-text" class="action-panel-label"> Optional text in email: </label> <textarea name="saved-search-email-text" id="saved-search-email-text" class="saved-search-email-text"></textarea> </div> </div> <div class="action-panel-actions"> <button class="action-panel-submit" type="submit" data-loading-label="Saving..." data-ga-category="save_share" data-ga-action="alert" data-ga-label="save"> Save </button> <button class="action-panel-cancel" aria-label="Close 'Your saved search' panel" ref="linksrc=close_saved_search_panel" aria-controls="saved-search-action-panel" aria-expanded="false" data-ga-category="save_share" data-ga-action="alert" data-ga-label="cancel"> Cancel </button> </div> </form> </div> </div> <div id="citation-manager-action-panel" class="citation-manager-action-panel action-panel" aria-hidden="true"> <div class="inner-wrap"> <h2 class="action-panel-heading"> Create a file for external citation management software </h2> <form id="citation-manager-action-panel-form" class="action-panel-content action-form" action="/results-export-ids/" data-by-search-action="/results-export-search-data/" data-by-ids-action="/results-export-ids/" method="post" data-by-search-method="post" data-by-ids-method="post"> <input type="hidden" name="csrfmiddlewaretoken" value="ecMLtYN8KWEyriFoSVIDayPIngWWftZaKdLdIsLYDl2JUf1iQZp2mTWsQ7jgLIIp"> <input name="results-format" type="hidden" value="pubmed"/> <div class="action-panel-actions"> <button class="action-panel-submit" type="submit" data-loading-label="Sending..." data-ga-category="save_share" data-ga-action="citation_manager" data-ga-label="save"> Create file </button> <button class="action-panel-cancel" aria-label="Close 'Send citations to citation manager' panel" ref="linksrc=close_citation_manager_panel" aria-controls="citation-manager-action-panel" aria-expanded="false" data-ga-category="save_share" data-ga-action="citation_manager" data-ga-label="cancel"> Cancel </button> </div> </form> </div> </div> <div id="rss-action-panel" class="rss-action-panel action-panel " aria-hidden="true"> <div class="inner-wrap"> <h2 class="action-panel-heading"> Your RSS Feed </h2> <form id="rss-action-panel-form" class="rss-action-panel-form action-panel-content action-form" data-create-rss-feed-url="/create-rss-feed-url/" data-search-form-term-value=""> <input type="hidden" name="csrfmiddlewaretoken" value="ecMLtYN8KWEyriFoSVIDayPIngWWftZaKdLdIsLYDl2JUf1iQZp2mTWsQ7jgLIIp"> <div class="action-panel-control-wrap"> <label for="rss-name" class="action-panel-label required-field-asterisk"> Name of RSS Feed: </label> <input maxlength="200" placeholder="Name" type="text" name="rss-name" id="rss-name" class="rss-name" value='' required pattern="[^"&=<>\/]*" title="The following characters are not allowed in the Name field: "&=<>/"> </div> <div class="rss-limit-wrap"> <div class="action-panel-control-wrap action-panel-extra-margin-top"> <label for="rss-limit" class="action-panel-label"> Number of items displayed: </label> <select id="rss-limit" class="no-border-panel-selector rss-limit"> <option value="5">5</option> <option value="10">10</option> <option value="15" selected="selected">15</option> <option value="20">20</option> <option value="50">50</option> <option value="100">100</option> </select> </div> </div> <div class="action-panel-actions"> <button class="action-panel-submit" type="submit" data-loading-label="Creating..." data-ga-category="save_share" data-ga-action="alert" data-ga-label="save"> Create RSS </button> <button class="action-panel-cancel" aria-label="Close 'Your RSS' panel" ref="linksrc=close_rss_panel" aria-controls="rss-action-panel" aria-expanded="false" data-ga-category="save_share" data-ga-action="alert" data-ga-label="cancel"> Cancel </button> </div> <div class="action-panel-control-wrap rss-link-copy-wrap"> <label for="rss-link" class="usa-sr-only">RSS Link</label> <input placeholder="Your RSS Feed Link" type="text" name="rss-link" id="rss-link" class="rss-link" title="RSS Link"> <button type="button" disabled class="rss-link-copy-button disabled" data-ga-category="save_share" data-ga-action="rss" data-ga-label="copy"> Copy </button> </div> </form> </div> </div> </div> </div> <div class="article-page" id="article-page" data-article-pmid="38947033"> <aside class="page-sidebar"> <div class="inner-wrap"> <div class="full-text-links"> <div class="full-view"> <h3 class="title"> Full text links </h3> <div class="full-text-links-list"> <a class="link-item dialog-focus" 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required-field-asterisk"> Name your collection: </label><input type="text" name="add-to-new-collection" id="collections-action-dialog-add-to-new" class="collections-action-add-to-new" pattern="[^"&=<>\/]*" title="The following characters are not allowed in the Name field: "&=<>/" maxlength="100" data-ga-category="collections_button" data-ga-action="create_collection" data-ga-label="non_favorties_collection"><div class="collections-new-name-too-long usa-input-error-message selection-validation-message"> Name must be less than 100 characters </div></div><div class="action-panel-control-wrap existing-collections-controls"><label for="collections-action-dialog-add-to-existing" class="action-panel-label"> Choose a collection: </label><select id="collections-action-dialog-add-to-existing" class="action-panel-selector collections-action-add-to-existing" data-ga-category="collections_button" data-ga-action="select_collection" data-ga-label="($('.collections-action-add-to-existing').val() === 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<div class="authors"> <div class="authors-list"> <span class="authors-list-item "><a class="full-name" href="/?term=Garc%C3%ADa-Gonz%C3%A1lez+J&cauthor_id=38947033" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Judit García-González">Judit García-González</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Department of Genetics and Genomic Sciences, Icahn School of Medicine, Mount Sinai, New York City, NY 10029, USA." href="#full-view-affiliation-1" ref="linksrc=author_aff"> 1 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Garcia-Gonzalez+S&cauthor_id=38947033" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Saul Garcia-Gonzalez">Saul Garcia-Gonzalez</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Department of Genetics and Genomic Sciences, Icahn School of Medicine, Mount Sinai, New York City, NY 10029, USA." href="#full-view-affiliation-1" ref="linksrc=author_aff"> 1 </a><span class="author-sup-separator"> </span><a class="affiliation-link" title="Center for Excellence in Youth Education, Icahn School of Medicine, Mount Sinai, New York City, NY 10029, USA." href="#full-view-affiliation-2" ref="linksrc=author_aff"> 2 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Liou+L&cauthor_id=38947033" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Lathan Liou">Lathan Liou</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Department of Genetics and Genomic Sciences, Icahn School of Medicine, Mount Sinai, New York City, NY 10029, USA." href="#full-view-affiliation-1" ref="linksrc=author_aff"> 1 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=O%27Reilly+PF&cauthor_id=38947033" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Paul F O'Reilly">Paul F O'Reilly</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Department of Genetics and Genomic Sciences, Icahn School of Medicine, Mount Sinai, New York City, NY 10029, USA." href="#full-view-affiliation-1" ref="linksrc=author_aff"> 1 </a></sup></span> </div> </div> </div> <div class="short-article-details"> Affiliations <button class="more-details" id="toggle-authors" data-alt-text="Collapse" aria-controls="expanded-authors" aria-expanded="false" data-pinger-ignore data-fetch-url="/38947033/long-authors/" data-id-prefix=""> <span class="title"> Expand </span> </button> </div> <div class="extended-article-details" id="expanded-authors" aria-hidden="true"> 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York City, NY 10029, USA." href="#short-view-affiliation-1" ref="linksrc=author_aff"> 1 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Garcia-Gonzalez+S&cauthor_id=38947033" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Saul Garcia-Gonzalez">Saul Garcia-Gonzalez</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Department of Genetics and Genomic Sciences, Icahn School of Medicine, Mount Sinai, New York City, NY 10029, USA." href="#short-view-affiliation-1" ref="linksrc=author_aff"> 1 </a><span class="author-sup-separator"> </span><a class="affiliation-link" title="Center for Excellence in Youth Education, Icahn School of Medicine, Mount Sinai, New York City, NY 10029, USA." href="#short-view-affiliation-2" ref="linksrc=author_aff"> 2 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Liou+L&cauthor_id=38947033" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Lathan Liou">Lathan Liou</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Department of Genetics and Genomic Sciences, Icahn School of Medicine, Mount Sinai, New York City, NY 10029, USA." href="#short-view-affiliation-1" ref="linksrc=author_aff"> 1 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=O%27Reilly+PF&cauthor_id=38947033" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Paul F O'Reilly">Paul F O'Reilly</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Department of Genetics and Genomic Sciences, Icahn School of Medicine, Mount Sinai, New York City, NY 10029, USA." href="#short-view-affiliation-1" ref="linksrc=author_aff"> 1 </a></sup></span> </div> </div> <div class="affiliations"> <h3 class="title"> Affiliations </h3> <ul class="item-list"> <li data-affiliation-id="short-view-affiliation-1" id="short-view-affiliation-1" ><sup class="key">1</sup> Department of Genetics and Genomic Sciences, Icahn School of Medicine, Mount Sinai, New York City, NY 10029, USA.</li> <li data-affiliation-id="short-view-affiliation-2" id="short-view-affiliation-2" ><sup class="key">2</sup> Center for Excellence in Youth Education, Icahn School of Medicine, Mount Sinai, New York City, NY 10029, USA.</li> </ul> </div> </div> <ul class="identifiers" id="short-view-identifiers"> <li> <span class="identifier pubmed"> <span class="id-label"> PMID: </span> <strong class="current-id" title="PubMed ID">38947033</strong> </span> </li> <li> <span class="identifier pmc"> <span class="id-label"> PMCID: </span> <a class="id-link" target="_blank" rel="noopener" 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id="inline-actions-display-format"><option value="abstract">Abstract</option><option value="pubmed">PubMed</option><option value="pmid">PMID</option></select></div></div></div></div></div></div> <div class="abstract" id="abstract"> <h2 class="title"> Abstract </h2> <div class="abstract-content selected" id="eng-abstract"> <p> Fine-mapping and gene-prioritisation techniques applied to the latest Genome-Wide Association Study (GWAS) results have prioritised hundreds of genes as causally associated with disease. Here we leverage these recently compiled lists of high-confidence causal genes to interrogate where in the body disease genes operate. Specifically, we combine GWAS summary statistics, gene prioritisation results and gene expression RNA-seq data from 46 tissues and 204 cell types in relation to 16 major diseases (including 8 cancers). In tissues and cell types with well-established relevance to the disease, the prioritised genes typically have higher absolute and relative (i.e. tissue/cell specific) expression compared to non-prioritised 'control' genes. Examples include brain tissues in psychiatric disorders (<i>P</i>-value < 1×10<sup>-7</sup>), microglia cells in Alzheimer's Disease (<i>P</i>-value = 9.8×10<sup>-3</sup>) and colon mucosa in colorectal cancer (<i>P</i>-value < 1×10<sup>-3</sup>). We also observe significantly higher expression for disease genes in multiple tissues and cell types with no established links to the corresponding disease. While some of these results may be explained by cell types that span multiple tissues, such as macrophages in brain, blood, lung and spleen in relation to Alzheimer's disease (<i>P</i>-values < 1×10<sup>-3</sup>), the cause for others is unclear and motivates further investigation that may provide novel insights into disease etiology. For example, mammary tissue in Type 2 Diabetes (<i>P</i>-value < 1×10<sup>-7</sup>); reproductive tissues such as breast, uterus, vagina, and prostate in Coronary Artery Disease (<i>P</i>-value < 1×10<sup>-4</sup>); and motor neurons in psychiatric disorders (<i>P</i>-value < 3×10<sup>-4</sup>). In the GTEx dataset, tissue type is the major predictor of gene expression but the contribution of each predictor (tissue, sample, subject, batch) varies widely among disease-associated genes. Finally, we highlight genes with the highest levels of gene expression in relevant tissues to guide functional follow-up studies. Our results could offer novel insights into the tissues and cells involved in disease initiation, inform drug target and delivery strategies, highlighting potential off-target effects, and exemplify the relative performance of different statistical tests for linking disease genes with tissue and cell type gene expression. </p> </div> </div> <p class="disclaimer" id="disclaimer"> <a href="/disclaimer/" target="_blank" ga_category="literature_resources" ga_action="disclaimer_link" ga_label="under_abstract">PubMed Disclaimer</a> </p> <div class="conflict-of-interest" id="conflict-of-interest"> <h2 class="title"> Conflict of interest statement </h2> <div class="statement"> <p xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:p1="http://pubmed.gov/pub-one">Competing interests The authors declare that they have no competing interests.</p> </div> </div> <div class="figures" id="figures"> <h2 class="title"> Figures </h2> <div class="figures-list" id="slides-container" itemscope itemtype="http://schema.org/ImageGallery"> <figure class="figure-item " itemscope itemtype="http://schema.org/ImageObject" itemprop="associatedMedia" data-slide-index="0" data-label-slug="figure-1"> <a class="figure-link" href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4624/11213058/c7cd413825ed/nihpp-2024.06.20.24309121v1-f0001.jpg" itemprop="contentUrl" aria-describedby="figure-caption-0" role="button" data-image-width="720" data-image-height="750" data-image-alt="Figure 1." data-pmc-id="PMC11213058" data-figure-id="F1"> <img class="figure-thumb" itemprop="thumbnail" id="article-image-0" src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4624/11213058/d9174804a353/nihpp-2024.06.20.24309121v1-f0001.gif" alt="Figure 1." /> </a> <meta itemprop="width" itemtype="http://schema.org/ImageObject" content="720"> <meta itemprop="height" itemtype="http://schema.org/ImageObject" content="750"> <div class="figure-caption figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="caption" aria-hidden="true"> <div class="caption-wrap"> <strong class="figure-label"> <p> Figure 1. </p> </strong> <div class="figure-caption-contents"><p> Overview of the study to… </p></div> </div> </div> <div class="figure-caption-medium figure-caption-text" aria-hidden="true"> <strong class="figure-label"> <p> Figure 1. </p> </strong> <div class="figure-caption-contents"><p> Overview of the study to characterise the gene expression features of genes associated… </p></div> </div> <figcaption id="figure-caption-0" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description"> <strong class="figure-label"> Figure 1. </strong> <div class="figure-caption-contents">Overview of the study to characterise the gene expression features of genes associated to diseases. <b>a</b>, Approach using lists putatively causal genes, prioritized based on GWAS results. <b>b</b>, Approach using genes with the highest absolute expression or highest relative expression in each tissue and cell type. <b>c</b>, PubMed-based literature search to assess the tissues that are most often cited for each disease. <b>d,</b> The approaches in a-c were repeated for the cell types and tissue regions available in the ARCHS4 and Tabula Sapiens resources. <b>e,</b> The predictors of gene expression were analysed for each gene using the variance partition R package. <b>f</b>, For each gene, absolute and relative gene expression was evaluated. Figure partially created with BioRender.com.</div> </figcaption> </figure> <figure class="figure-item " itemscope itemtype="http://schema.org/ImageObject" itemprop="associatedMedia" data-slide-index="1" data-label-slug="figure-2"> <a class="figure-link" href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4624/11213058/02424a24f401/nihpp-2024.06.20.24309121v1-f0002.jpg" itemprop="contentUrl" aria-describedby="figure-caption-1" role="button" data-image-width="664" data-image-height="899" data-image-alt="Figure 2." data-pmc-id="PMC11213058" data-figure-id="F2"> <img class="figure-thumb" itemprop="thumbnail" id="article-image-1" src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4624/11213058/d9f5750ffcd4/nihpp-2024.06.20.24309121v1-f0002.gif" alt="Figure 2." /> </a> <meta itemprop="width" itemtype="http://schema.org/ImageObject" content="664"> <meta itemprop="height" itemtype="http://schema.org/ImageObject" content="899"> <div class="figure-caption figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="caption" aria-hidden="true"> <div class="caption-wrap"> <strong class="figure-label"> <p> Figure 2. </p> </strong> <div class="figure-caption-contents"><p> Heatmap showing results of the… </p></div> </div> </div> <div class="figure-caption-medium figure-caption-text" aria-hidden="true"> <strong class="figure-label"> <p> Figure 2. </p> </strong> <div class="figure-caption-contents"><p> Heatmap showing results of the association between gene expression in each GTEx tissue… </p></div> </div> <figcaption id="figure-caption-1" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description"> <strong class="figure-label"> Figure 2. </strong> <div class="figure-caption-contents">Heatmap showing results of the association between gene expression in each GTEx tissue and <b>a</b>, Schizophrenia; <b>b</b>, Coronary Artery Disease; <b>c</b>, Alzheimer’s Disease; <b>d</b>, Inflammatory Bowel Disease; <b>e</b>, Bipolar Disorder; <b>f</b>, ADHD; <b>g,</b> Type 2 Diabetes; <b>h</b>, Vitamin D. In blue, results showing the Log<sub>10</sub> <i>P</i>-value for a one-side <i>t</i>-tests, testing the null hypothesis that disease-associated genes are not more expressed than other protein-coding genes expressed in that tissue. In red, results showing the Log<sub>10</sub> <i>P</i>-value for enrichment of GWAS signal across the set of genes with highest absolute and relative expression for each tissue. In yellow, results for the Literature Search using PubMed. Abs. Exp, Absolute expression; Rel. Relative expression; F, Fine-mapped genes; N, Nearest-to-hit genes, P, Polygenic Priority Scores genes; Title & Abst, Title and Abstract; MeSH, MeSH terms.</div> </figcaption> </figure> <figure class="figure-item " itemscope itemtype="http://schema.org/ImageObject" itemprop="associatedMedia" data-slide-index="2" data-label-slug="figure-2"> <a class="figure-link" href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4624/11213058/45e976a96b9c/nihpp-2024.06.20.24309121v1-f0003.jpg" itemprop="contentUrl" aria-describedby="figure-caption-2" role="button" data-image-width="640" data-image-height="899" data-image-alt="Figure 2." data-pmc-id="PMC11213058" data-figure-id="F2"> <img class="figure-thumb" itemprop="thumbnail" id="article-image-2" src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4624/11213058/d9f5750ffcd4/nihpp-2024.06.20.24309121v1-f0002.gif" alt="Figure 2." /> </a> <meta itemprop="width" itemtype="http://schema.org/ImageObject" content="640"> <meta itemprop="height" itemtype="http://schema.org/ImageObject" content="899"> <div class="figure-caption figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="caption" aria-hidden="true"> <div class="caption-wrap"> <strong class="figure-label"> <p> Figure 2. </p> </strong> <div class="figure-caption-contents"><p> Heatmap showing results of the… </p></div> </div> </div> <div class="figure-caption-medium figure-caption-text" aria-hidden="true"> <strong class="figure-label"> <p> Figure 2. </p> </strong> <div class="figure-caption-contents"><p> Heatmap showing results of the association between gene expression in each GTEx tissue… </p></div> </div> <figcaption id="figure-caption-2" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description"> <strong class="figure-label"> Figure 2. </strong> <div class="figure-caption-contents">Heatmap showing results of the association between gene expression in each GTEx tissue and <b>a</b>, Schizophrenia; <b>b</b>, Coronary Artery Disease; <b>c</b>, Alzheimer’s Disease; <b>d</b>, Inflammatory Bowel Disease; <b>e</b>, Bipolar Disorder; <b>f</b>, ADHD; <b>g,</b> Type 2 Diabetes; <b>h</b>, Vitamin D. In blue, results showing the Log<sub>10</sub> <i>P</i>-value for a one-side <i>t</i>-tests, testing the null hypothesis that disease-associated genes are not more expressed than other protein-coding genes expressed in that tissue. In red, results showing the Log<sub>10</sub> <i>P</i>-value for enrichment of GWAS signal across the set of genes with highest absolute and relative expression for each tissue. In yellow, results for the Literature Search using PubMed. Abs. Exp, Absolute expression; Rel. Relative expression; F, Fine-mapped genes; N, Nearest-to-hit genes, P, Polygenic Priority Scores genes; Title & Abst, Title and Abstract; MeSH, MeSH terms.</div> </figcaption> </figure> <figure class="figure-item " itemscope itemtype="http://schema.org/ImageObject" itemprop="associatedMedia" data-slide-index="3" data-label-slug="figure-3"> <a class="figure-link" href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4624/11213058/c5b1026ddedf/nihpp-2024.06.20.24309121v1-f0004.jpg" itemprop="contentUrl" aria-describedby="figure-caption-3" role="button" data-image-width="695" data-image-height="899" data-image-alt="Figure 3." data-pmc-id="PMC11213058" data-figure-id="F3"> <img class="figure-thumb" itemprop="thumbnail" id="article-image-3" src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4624/11213058/464cb2670706/nihpp-2024.06.20.24309121v1-f0004.gif" alt="Figure 3." /> </a> <meta itemprop="width" itemtype="http://schema.org/ImageObject" content="695"> <meta itemprop="height" itemtype="http://schema.org/ImageObject" content="899"> <div class="figure-caption figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="caption" aria-hidden="true"> <div class="caption-wrap"> <strong class="figure-label"> <p> Figure 3. </p> </strong> <div class="figure-caption-contents"><p> Heatmap showing results of the… </p></div> </div> </div> <div class="figure-caption-medium figure-caption-text" aria-hidden="true"> <strong class="figure-label"> <p> Figure 3. </p> </strong> <div class="figure-caption-contents"><p> Heatmap showing results of the association between gene expression in each cell-type obtained… </p></div> </div> <figcaption id="figure-caption-3" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description"> <strong class="figure-label"> Figure 3. </strong> <div class="figure-caption-contents">Heatmap showing results of the association between gene expression in each cell-type obtained from the Tabula Sapiens dataset <b>a</b>, Tabula Sapiens datasets were downloaded for each tissue, and absolute and relative expression was calculated for each cell type in each tissue. <b>b</b>, Results for Coronary Artery Disease. <b>c</b>, Results for Inflammatory Bowel Disease. <b>d</b>. Results for Vitamin D. In blue, results showing the Log<sub>10</sub> empirical <i>P</i>-value after running 10,000 permutations, testing the null hypothesis that disease-associated genes are not more expressed than other protein-coding genes expressed in that tissue. In red, results showing the Log<sub>10</sub> <i>P</i>-value for enrichment of GWAS signal across the set of genes with highest expression for each tissue. In yellow, results for the Literature Search using PubMed. Abs. Exp, Absolute expression; Rel. Exp, relative expression; F, Fine-mapped genes; N, Nearest-to-hit genes, P, Polygenic Priority Scores genes; Title & Abst, Title and Abstract are used in the PubMed Search.</div> </figcaption> </figure> <figure class="figure-item " itemscope itemtype="http://schema.org/ImageObject" itemprop="associatedMedia" data-slide-index="4" data-label-slug="figure-4"> <a class="figure-link" href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4624/11213058/c0984a61eae6/nihpp-2024.06.20.24309121v1-f0005.jpg" itemprop="contentUrl" aria-describedby="figure-caption-4" role="button" data-image-width="699" data-image-height="899" data-image-alt="Figure 4." data-pmc-id="PMC11213058" data-figure-id="F4"> <img class="figure-thumb" itemprop="thumbnail" id="article-image-4" src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4624/11213058/728b535fde8f/nihpp-2024.06.20.24309121v1-f0005.gif" alt="Figure 4." /> </a> <meta itemprop="width" itemtype="http://schema.org/ImageObject" content="699"> <meta itemprop="height" itemtype="http://schema.org/ImageObject" content="899"> <div class="figure-caption figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="caption" aria-hidden="true"> <div class="caption-wrap"> <strong class="figure-label"> <p> Figure 4. </p> </strong> <div class="figure-caption-contents"><p> Heatmap showing results of the… </p></div> </div> </div> <div class="figure-caption-medium figure-caption-text" aria-hidden="true"> <strong class="figure-label"> <p> Figure 4. </p> </strong> <div class="figure-caption-contents"><p> Heatmap showing results of the association between gene expression in each cell-type obtained… </p></div> </div> <figcaption id="figure-caption-4" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description"> <strong class="figure-label"> Figure 4. </strong> <div class="figure-caption-contents">Heatmap showing results of the association between gene expression in each cell-type obtained from the Tabula Sapiens dataset. <b>a</b>, Results using RNA-seq data from cell types and tissue regions extracted from the ARCHS4 resources. <b>b</b>, Results using RNA-seq data from the Tabula Sapiens for blood (red section), spleen (blue section), and fat (yellow section).</div> </figcaption> </figure> <figure class="figure-item " itemscope itemtype="http://schema.org/ImageObject" itemprop="associatedMedia" data-slide-index="5" data-label-slug="figure-5"> <a class="figure-link" href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4624/11213058/2c32f5b2333d/nihpp-2024.06.20.24309121v1-f0006.jpg" itemprop="contentUrl" aria-describedby="figure-caption-5" role="button" data-image-width="647" data-image-height="899" data-image-alt="Figure 5." data-pmc-id="PMC11213058" data-figure-id="F5"> <img class="figure-thumb" itemprop="thumbnail" id="article-image-5" src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4624/11213058/08202002f849/nihpp-2024.06.20.24309121v1-f0006.gif" alt="Figure 5." /> </a> <meta itemprop="width" itemtype="http://schema.org/ImageObject" content="647"> <meta itemprop="height" itemtype="http://schema.org/ImageObject" content="899"> <div class="figure-caption figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="caption" aria-hidden="true"> <div class="caption-wrap"> <strong class="figure-label"> <p> Figure 5.. Variance partition is used to… </p> </strong> </div> </div> <div class="figure-caption-medium figure-caption-text" aria-hidden="true"> <strong class="figure-label"> <p> Figure 5.. Variance partition is used to investigate the factors influencing gene expression of disease-associated… </p> </strong> </div> <figcaption id="figure-caption-5" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description"> <strong class="figure-label"> Figure 5.. Variance partition is used to investigate the factors influencing gene expression of disease-associated genes. </strong> <div class="figure-caption-contents"><b>a,</b> Violin plots representing the distribution of variance partition across all disease-associated genes for the eight diseases investigated. <b>b,</b> variance partition results for genes associated with schizophrenia. Genes labelled represent: two genes encoding protein phosphatases (PPP2R3A & PPP2R2B) where tissue-type explain a large fraction in gene expression variance, and a gene (STAB1) where tissue explains less than 10% in gene expression variance. The dopamine receptor 2 (DRD2) is also included because it is the main receptor for most antipsychotic drugs<sup>,</sup>. <b>c,</b> Bar plots of individual genes showing the variance partition estimates at the individual gene level for genes highlighted in panel b, <b>d,</b> Violin plots showing the differences in variance partition results between disease-associated genes and control genes.</div> </figcaption> </figure> <figure class="figure-item tail" itemscope itemtype="http://schema.org/ImageObject" itemprop="associatedMedia" data-slide-index="6" data-label-slug="figure-6"> <a class="figure-link" href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4624/11213058/15d3b14960ce/nihpp-2024.06.20.24309121v1-f0007.jpg" itemprop="contentUrl" aria-describedby="figure-caption-6" role="button" data-image-width="720" data-image-height="439" data-image-alt="Figure 6." data-pmc-id="PMC11213058" data-figure-id="F6"> <img class="figure-thumb" itemprop="thumbnail" id="article-image-6" src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4624/11213058/a91927b12112/nihpp-2024.06.20.24309121v1-f0007.gif" alt="Figure 6." /> </a> <meta itemprop="width" itemtype="http://schema.org/ImageObject" content="720"> <meta itemprop="height" itemtype="http://schema.org/ImageObject" content="439"> <div class="figure-caption figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="caption" aria-hidden="true"> <div class="caption-wrap"> <strong class="figure-label"> <p> Figure 6.. Exploring disease-associated genes showing both… </p> </strong> </div> </div> <div class="figure-caption-medium figure-caption-text" aria-hidden="true"> <strong class="figure-label"> <p> Figure 6.. Exploring disease-associated genes showing both high absolute and high relative expression. </p> </strong> <div class="figure-caption-contents"><p> Scatter plots… </p></div> </div> <figcaption id="figure-caption-6" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description"> <strong class="figure-label"> Figure 6.. Exploring disease-associated genes showing both high absolute and high relative expression. </strong> <div class="figure-caption-contents">Scatter plots showing the relationship between absolute gene expression and relative gene expression in disease-associated genes. Only the tissue with the most significant differences between disease-associated and control genes is shown.</div> </figcaption> </figure> </div> <div class="see-all actions-bar"> <button class="show-more" aria-controls="slides-container" data-ga-category="figure" data-ga-action="show_all"> All figures (7) </button> </div>  <div class="pswp figures-dialog" id="figures-dialog" tabindex="-1" role="dialog" aria-hidden="true" data-image-gallery-uid="article-figures" aria-label="Figures Dialog">  <div class="pswp__bg"></div>  <div class="pswp__scroll-wrap">  <div class="pswp__container"> <div class="pswp__item"></div> <div class="pswp__item"></div> <div class="pswp__item"></div> </div>  <div class="pswp__ui pswp__ui--hidden"> <div class="pswp__top-bar">  <div class="pswp__counter"></div> <button class="pswp__button pswp__button--close" title="Close (Esc)"></button> <button class="pswp__button pswp__button--share" title="Share"></button> <button class="pswp__button pswp__button--fs" 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The Gene Expression Landscape of Disease Genes - PubMed