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(PDF) Identification and Replication of Three Novel Myopia Common Susceptibility Gene Loci on Chromosome 3q26 using Linkage and Linkage Disequilibrium Mapping
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Following an initial genomewide linkage study using microsatellite markers, we confirmed evidence for linkage to chromosome 3q26 and then conducted" /> <meta name="twitter:image" content="http://a.academia-assets.com/images/twitter-card.jpeg" /> <meta property="fb:app_id" content="2369844204" /> <meta property="og:type" content="article" /> <meta property="og:url" content="https://www.academia.edu/18362529/Identification_and_Replication_of_Three_Novel_Myopia_Common_Susceptibility_Gene_Loci_on_Chromosome_3q26_using_Linkage_and_Linkage_Disequilibrium_Mapping" /> <meta property="og:title" content="Identification and Replication of Three Novel Myopia Common Susceptibility Gene Loci on Chromosome 3q26 using Linkage and Linkage Disequilibrium Mapping" /> <meta property="og:image" content="http://a.academia-assets.com/images/open-graph-icons/fb-paper.gif" /> <meta property="og:description" content="Refractive error is a highly heritable quantitative trait responsible for considerable morbidity. Following an initial genomewide linkage study using microsatellite markers, we confirmed evidence for linkage to chromosome 3q26 and then conducted" /> <meta property="article:author" content="https://independent.academia.edu/FrancisCarbonaro" /> <meta property="article:author" content="https://independent.academia.edu/WinstonLau" /> <meta name="description" content="Refractive error is a highly heritable quantitative trait responsible for considerable morbidity. Following an initial genomewide linkage study using microsatellite markers, we confirmed evidence for linkage to chromosome 3q26 and then conducted" /> <title>(PDF) Identification and Replication of Three Novel Myopia Common Susceptibility Gene Loci on Chromosome 3q26 using Linkage and Linkage Disequilibrium Mapping</title> <link rel="canonical" href="https://www.academia.edu/18362529/Identification_and_Replication_of_Three_Novel_Myopia_Common_Susceptibility_Gene_Loci_on_Chromosome_3q26_using_Linkage_and_Linkage_Disequilibrium_Mapping" /> <script async src="https://www.googletagmanager.com/gtag/js?id=G-5VKX33P2DS"></script> <script> window.dataLayer = window.dataLayer || []; function gtag(){dataLayer.push(arguments);} gtag('js', new Date()); gtag('config', 'G-5VKX33P2DS', { cookie_domain: 'academia.edu', send_page_view: false, }); gtag('event', 'page_view', { 'controller': "single_work", 'action': "show", 'controller_action': 'single_work#show', 'logged_in': 'false', 'edge': 'unknown', 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Date().getTime() - 1740212851000; </script> <script type="application/ld+json">{"@context":"https://schema.org","@type":"ScholarlyArticle","author":[{"@context":"https://schema.org","@type":"Person","name":"Francis Carbonaro","url":"https://independent.academia.edu/FrancisCarbonaro"},{"@context":"https://schema.org","@type":"Person","name":"Winston Lau","url":"https://independent.academia.edu/WinstonLau"}],"contributor":[{"@context":"https://schema.org","@type":"Person","name":"Winston Lau","url":"https://independent.academia.edu/WinstonLau"}],"dateCreated":"2015-11-14","dateModified":"2024-11-28","datePublished":"2008-01-01","headline":"Identification and Replication of Three Novel Myopia Common Susceptibility Gene Loci on Chromosome 3q26 using Linkage and Linkage Disequilibrium Mapping","image":"https://attachments.academia-assets.com/40014317/thumbnails/1.jpg","inLanguage":"en","keywords":["Genetics","Myopia","Molecular Genetics","Adolescent","Transcription Factors","Refractive 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{"work":{"id":18362529,"created_at":"2015-11-14T22:58:05.702-08:00","from_world_paper_id":144459550,"updated_at":"2024-11-28T05:24:12.046-08:00","_data":{"ai_title_tag":"Novel Myopia Gene Loci on Chromosome 3q26 Identified and Replicated","grobid_abstract":"Refractive error is a highly heritable quantitative trait responsible for considerable morbidity. Following an initial genomewide linkage study using microsatellite markers, we confirmed evidence for linkage to chromosome 3q26 and then conducted fine-scale association mapping using high-resolution linkage disequilibrium unit (LDU) maps. We used a preliminary discovery marker set across the 30-Mb region with an average SNP density of 1 SNP/15 kb (Map 1). Map 1 was divided into 51 LDU windows and additional SNPs were genotyped for six regions (Map 2) that showed preliminary evidence of multi-marker association using composite likelihood. A total of 575 cases and controls selected from the tails of the trait distribution were genotyped for the discovery sample. Malecot model estimates indicate three loci with putative common functional variants centred on MFN1 (180,566 kb; 95% confidence interval 180,505-180, 655 kb), approximately 156 kb upstream from alternate-splicing SOX2OT (182,595 kb; 95% CI 182,533-182,688 kb) and PSARL (184,386 kb; 95% CI 184,411 kb), with the loci showing modest to strong evidence of association for the Map 2 discovery samples (p,10 27 , p,10 210 , and p = 0.01, respectively). Using an unselected independent sample of 1,430 individuals, results replicated for the MFN1 (p = 0.006), SOX2OT (p = 0.0002), and PSARL (p = 0.0005) gene regions. MFN1 and PSARL both interact with OPA1 to regulate mitochondrial fusion and the inhibition of mitochondrial-led apoptosis, respectively. That two mitochondrial regulatory processes in the retina are implicated in the aetiology of myopia is surprising and is likely to provide novel insight into the molecular genetic basis of common myopia.","publication_date":"2008,,","publication_name":"PLoS Genetics","grobid_abstract_attachment_id":"40014317"},"document_type":"paper","pre_hit_view_count_baseline":null,"quality":"high","language":"en","title":"Identification and Replication of Three Novel Myopia Common Susceptibility Gene Loci on Chromosome 3q26 using Linkage and Linkage Disequilibrium Mapping","broadcastable":false,"draft":null,"has_indexable_attachment":true,"indexable":true}}["work"]; window.loswp.workCoauthors = [38671459,38352462]; window.loswp.locale = "en"; window.loswp.countryCode = "SG"; window.loswp.cwvAbTestBucket = ""; window.loswp.designVariant = "ds_vanilla"; window.loswp.fullPageMobileSutdModalVariant = "control"; window.loswp.useOptimizedScribd4genScript = false; window.loginModal = {}; window.loginModal.appleClientId = 'edu.academia.applesignon'; window.userInChina = "false";</script><script defer="" src="https://accounts.google.com/gsi/client"></script><div class="ds-loswp-container"><div class="ds-work-card--grid-container"><div class="ds-work-card--container js-loswp-work-card"><div class="ds-work-card--cover"><div class="ds-work-cover--wrapper"><div class="ds-work-cover--container"><button class="ds-work-cover--clickable js-swp-download-button" data-signup-modal="{"location":"swp-splash-paper-cover","attachmentId":40014317,"attachmentType":"pdf"}"><img alt="First page of “Identification and Replication of Three Novel Myopia Common Susceptibility Gene Loci on Chromosome 3q26 using Linkage and Linkage Disequilibrium Mapping”" class="ds-work-cover--cover-thumbnail" src="https://0.academia-photos.com/attachment_thumbnails/40014317/mini_magick20190222-13827-1a1jgpa.png?1550827788" /><img alt="PDF Icon" class="ds-work-cover--file-icon" src="//a.academia-assets.com/images/single_work_splash/adobe_icon.svg" /><div class="ds-work-cover--hover-container"><span class="material-symbols-outlined" style="font-size: 20px" translate="no">download</span><p>Download Free PDF</p></div><div class="ds-work-cover--ribbon-container">Download Free PDF</div><div class="ds-work-cover--ribbon-triangle"></div></button></div></div></div><div class="ds-work-card--work-information"><h1 class="ds-work-card--work-title">Identification and Replication of Three Novel Myopia Common Susceptibility Gene Loci on Chromosome 3q26 using Linkage and Linkage Disequilibrium Mapping</h1><div class="ds-work-card--work-authors ds-work-card--detail"><a class="ds-work-card--author js-wsj-grid-card-author ds2-5-body-md ds2-5-body-link" data-author-id="38671459" href="https://independent.academia.edu/WinstonLau"><img alt="Profile image of Winston Lau" class="ds-work-card--author-avatar" src="//a.academia-assets.com/images/s65_no_pic.png" />Winston Lau</a><a class="ds-work-card--author js-wsj-grid-card-author ds2-5-body-md ds2-5-body-link" data-author-id="38352462" href="https://independent.academia.edu/FrancisCarbonaro"><img alt="Profile image of Francis Carbonaro" class="ds-work-card--author-avatar" src="//a.academia-assets.com/images/s65_no_pic.png" />Francis Carbonaro</a></div><div class="ds-work-card--detail"><p class="ds-work-card--detail ds2-5-body-sm">2008, PLoS Genetics</p><div class="ds-work-card--work-metadata"><div class="ds-work-card--work-metadata__stat"><span class="material-symbols-outlined" style="font-size: 20px" translate="no">visibility</span><p class="ds2-5-body-sm" id="work-metadata-view-count">…</p></div><div class="ds-work-card--work-metadata__stat"><span class="material-symbols-outlined" style="font-size: 20px" translate="no">description</span><p class="ds2-5-body-sm">11 pages</p></div><div class="ds-work-card--work-metadata__stat"><span class="material-symbols-outlined" style="font-size: 20px" translate="no">link</span><p class="ds2-5-body-sm">1 file</p></div></div><script>(async () => { const workId = 18362529; 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if (!viewCountBody) { throw new Error('Failed to find work views element'); } viewCountBody.textContent = `${commaizedViewCount} views`; } catch (error) { // Remove the whole views element if there was some issue parsing. document.getElementById('work-metadata-view-count')?.parentNode?.remove(); throw new Error(`Failed to parse view count: ${viewCount}`, error); } }; // If the DOM is still loading, wait for it to be ready before updating the view count. if (document.readyState === "loading") { document.addEventListener('DOMContentLoaded', () => { updateViewCount(viewCount); }); // Otherwise, just update it immediately. } else { updateViewCount(viewCount); } })();</script></div><p class="ds-work-card--work-abstract ds-work-card--detail ds2-5-body-md">Refractive error is a highly heritable quantitative trait responsible for considerable morbidity. Following an initial genomewide linkage study using microsatellite markers, we confirmed evidence for linkage to chromosome 3q26 and then conducted fine-scale association mapping using high-resolution linkage disequilibrium unit (LDU) maps. We used a preliminary discovery marker set across the 30-Mb region with an average SNP density of 1 SNP/15 kb (Map 1). Map 1 was divided into 51 LDU windows and additional SNPs were genotyped for six regions (Map 2) that showed preliminary evidence of multi-marker association using composite likelihood. A total of 575 cases and controls selected from the tails of the trait distribution were genotyped for the discovery sample. Malecot model estimates indicate three loci with putative common functional variants centred on MFN1 (180,566 kb; 95% confidence interval 180,505-180, 655 kb), approximately 156 kb upstream from alternate-splicing SOX2OT (182,595 kb; 95% CI 182,533-182,688 kb) and PSARL (184,386 kb; 95% CI 184,411 kb), with the loci showing modest to strong evidence of association for the Map 2 discovery samples (p,10 27 , p,10 210 , and p = 0.01, respectively). Using an unselected independent sample of 1,430 individuals, results replicated for the MFN1 (p = 0.006), SOX2OT (p = 0.0002), and PSARL (p = 0.0005) gene regions. MFN1 and PSARL both interact with OPA1 to regulate mitochondrial fusion and the inhibition of mitochondrial-led apoptosis, respectively. That two mitochondrial regulatory processes in the retina are implicated in the aetiology of myopia is surprising and is likely to provide novel insight into the molecular genetic basis of common myopia.</p><div class="ds-work-card--button-container"><button class="ds2-5-button js-swp-download-button" data-signup-modal="{"location":"continue-reading-button--work-card","attachmentId":40014317,"attachmentType":"pdf","workUrl":"https://www.academia.edu/18362529/Identification_and_Replication_of_Three_Novel_Myopia_Common_Susceptibility_Gene_Loci_on_Chromosome_3q26_using_Linkage_and_Linkage_Disequilibrium_Mapping"}">See full PDF</button><button class="ds2-5-button ds2-5-button--secondary js-swp-download-button" data-signup-modal="{"location":"download-pdf-button--work-card","attachmentId":40014317,"attachmentType":"pdf","workUrl":"https://www.academia.edu/18362529/Identification_and_Replication_of_Three_Novel_Myopia_Common_Susceptibility_Gene_Loci_on_Chromosome_3q26_using_Linkage_and_Linkage_Disequilibrium_Mapping"}"><span class="material-symbols-outlined" style="font-size: 20px" translate="no">download</span>Download PDF</button></div><div class="ds-signup-banner-trigger-container"><div class="ds-signup-banner-trigger ds-signup-banner-trigger-control"></div></div><div class="ds-signup-banner ds-signup-banner-control"><div id="ds-signup-banner-close-button"><button class="ds2-5-button ds2-5-button--secondary ds2-5-button--inverse"><span class="material-symbols-outlined" style="font-size: 20px" translate="no">close</span></button></div><div class="ds-signup-banner-ctas"><img src="//a.academia-assets.com/images/academia-logo-capital-white.svg" /><h4 class="ds2-5-heading-serif-sm">Sign up for access to the world's latest research</h4><button class="ds2-5-button ds2-5-button--inverse ds2-5-button--full-width js-swp-download-button" data-signup-modal="{"location":"signup-banner"}">Sign up for free<span class="material-symbols-outlined" style="font-size: 20px" translate="no">arrow_forward</span></button></div><div class="ds-signup-banner-divider"></div><div class="ds-signup-banner-reasons"><div class="ds-signup-banner-reasons-item"><span class="material-symbols-outlined" style="font-size: 24px" translate="no">check</span><span>Get notified about relevant papers</span></div><div class="ds-signup-banner-reasons-item"><span class="material-symbols-outlined" style="font-size: 24px" translate="no">check</span><span>Save papers to use in your research</span></div><div class="ds-signup-banner-reasons-item"><span class="material-symbols-outlined" style="font-size: 24px" translate="no">check</span><span>Join the discussion with peers</span></div><div class="ds-signup-banner-reasons-item"><span class="material-symbols-outlined" style="font-size: 24px" translate="no">check</span><span>Track your impact</span></div></div></div><script>(() => { // Set up signup banner show/hide behavior: // 1. 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Genetic and environmental factors contribute to the development of myopia. Studies on the molecular genetics of myopia are well established and have implicated the important role of genetic factors. With linkage analysis, association studies, sequencing analysis, and experimental myopia studies, many of the loci and genes associated with myopia have been identified. Thus far, there has been no systemic review of the loci and genes related to non-syndromic and syndromic myopia based on the different approaches. Such a systemic review of the molecular genetics of myopia will provide clues to identify additional plausible genes for myopia and help us to understand the molecular mechanisms underlying myopia. This paper reviews recent genetic studies on myopia, summarizes all possible reported genes and loci related to myopia, and suggests implications for future studies on the molecular genetics of myopia.</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Insight into the molecular genetics of myopia","attachmentId":80499750,"attachmentType":"pdf","work_url":"https://www.academia.edu/70966007/Insight_into_the_molecular_genetics_of_myopia","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/70966007/Insight_into_the_molecular_genetics_of_myopia"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="1" data-entity-id="66325736" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/66325736/A_genome_wide_scan_for_familial_high_myopia_suggests_a_novel_locus_on_chromosome_7q36">A genome wide scan for familial high myopia suggests a novel locus on chromosome 7q36</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="37458324" href="https://independent.academia.edu/OlivierRascol">Olivier Rascol</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Journal of Medical Genetics, 2002</p><p class="ds-related-work--abstract ds2-5-body-sm">laboratory, in order to validate these results and to reduce the critical region for high myopia. The recruitment and analysis of new families and/or new members of the families already studied are needed before starting gene isolation experiments. The characterisation of the genes implicated in this common eye disorder will lead to a better understanding of the molecular mechanisms contributing to eye shape and growth. ACKNOWLEDGEMENTS Electronic database information. URLs for data in this paper are as follows: Perkin-Elmer, http://www.pebio.com/ga/ (for ABI PRISM Linkage Mapping Set MD-10). Généthon, http://genethon.fr (for additional polymorphic markers). CHLC Genetic maps, http://chlc.org/ ChlcMaps.html (for additional polymorphic markers). Human Gene Map '99, http://www.ncbi.nlm.nih.gov/genemap99 (for genes and expressed sequence tags in the region of interest within the interval between marker D7S798 and the telomere). We thank Dr L Cardon for his helpful discussion and for contributing actively to the statistical part of this work and Professor A Hovnanian for his critical review and comments on the manuscript. We also extend many thanks to the members of the myopia families. This work was supported by grants from the Association Retina France and from INSERM: Programme de Recherche en Santé No 4P015D.</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"A genome wide scan for familial high myopia suggests a novel locus on chromosome 7q36","attachmentId":77563405,"attachmentType":"pdf","work_url":"https://www.academia.edu/66325736/A_genome_wide_scan_for_familial_high_myopia_suggests_a_novel_locus_on_chromosome_7q36","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/66325736/A_genome_wide_scan_for_familial_high_myopia_suggests_a_novel_locus_on_chromosome_7q36"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="2" data-entity-id="55116886" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/55116886/Novel_Myopia_Genes_and_Pathways_Identified_From_Syndromic_Forms_of_Myopia">Novel Myopia Genes and Pathways Identified From Syndromic Forms of Myopia</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="36751393" href="https://independent.academia.edu/JamesLoughman">James Loughman</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Investigative ophthalmology & visual science, 2018</p><p class="ds-related-work--abstract ds2-5-body-sm">To test the hypothesis that genes known to cause clinical syndromes featuring myopia also harbor polymorphisms contributing to nonsyndromic refractive errors. Clinical phenotypes and syndromes that have refractive errors as a recognized feature were identified using the Online Mendelian Inheritance in Man (OMIM) database. One hundred fifty-four unique causative genes were identified, of which 119 were specifically linked with myopia and 114 represented syndromic myopia (i.e., myopia and at least one other clinical feature). Myopia was the only refractive error listed for 98 genes and hyperopia and the only refractive error noted for 28 genes, with the remaining 28 genes linked to phenotypes with multiple forms of refractive error. Pathway analysis was carried out to find biological processes overrepresented within these sets of genes. Genetic variants located within 50 kb of the 119 myopia-related genes were evaluated for involvement in refractive error by analysis of summary statis...</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Novel Myopia Genes and Pathways Identified From Syndromic Forms of Myopia","attachmentId":71143801,"attachmentType":"pdf","work_url":"https://www.academia.edu/55116886/Novel_Myopia_Genes_and_Pathways_Identified_From_Syndromic_Forms_of_Myopia","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/55116886/Novel_Myopia_Genes_and_Pathways_Identified_From_Syndromic_Forms_of_Myopia"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="3" data-entity-id="60958491" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/60958491/Replication_study_of_significant_single_nucleotide_polymorphisms_associated_with_myopia_from_two_genome_wide_association_studies">Replication study of significant single nucleotide polymorphisms associated with myopia from two genome-wide association studies</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="45139348" href="https://independent.academia.edu/QingjiongZhang">Qingjiong Zhang</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Molecular vision, 2011</p><p class="ds-related-work--abstract ds2-5-body-sm">Two previous genome-wide association studies (GWAS) of high myopia in a Japanese population found several single nucleotide polymorphisms (SNPs) associated with the disease. The present study examined whether these markers are associated with myopia in a Chinese population. Individuals with or without complex myopia were recruited from Chinese university students, and probands with early onset high myopia were identified in the Pediatric and Genetic Eye Clinic of the Zhongshan Ophthalmic Center. DNA was prepared from venous leukocytes. Three SNPs, rs577948 and rs11218544 at chromosome position 11q24.1 and rs2839471 at chromosome position 21q22.3, were genotyped. The allele and genotype frequencies of these SNPs were compared between the myopia cases and controls using a χ(2) test. A total of 2,870 subjects were examined in this study, including 1,255 individuals with complex myopia (-10.00 diopter (D)&lt;spherical refraction≤-4.00 D), 563 with early onset high myopia (spherical refr...</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Replication study of significant single nucleotide polymorphisms associated with myopia from two genome-wide association studies","attachmentId":74174978,"attachmentType":"pdf","work_url":"https://www.academia.edu/60958491/Replication_study_of_significant_single_nucleotide_polymorphisms_associated_with_myopia_from_two_genome_wide_association_studies","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/60958491/Replication_study_of_significant_single_nucleotide_polymorphisms_associated_with_myopia_from_two_genome_wide_association_studies"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="4" data-entity-id="14485103" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/14485103/A_genome_wide_association_study_for_myopia_and_refractive_error_identifies_a_susceptibility_locus_at_15q25">A genome-wide association study for myopia and refractive error identifies a susceptibility locus at 15q25</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="33429686" href="https://independent.academia.edu/EugenioSantos2">Eugenio Santos</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Nature Genetics, 2010</p><p class="ds-related-work--abstract ds2-5-body-sm">l e t t e r s Myopia and hyperopia are at opposite ends of the continuum of refraction, the measure of the eye′s ability to focus light, which is an important cause of visual impairment (when aberrant) and is a highly heritable trait. We conducted a genome-wide association study for refractive error in 4,270 individuals from the TwinsUK cohort. We identified SNPs on 15q25 associated with refractive error (rs8027411, P = 7.91 × 10 −8 ). We replicated this association in six adult cohorts of European ancestry with a combined 13,414 individuals (combined P = 2.07 × 10 −9 ). This locus overlaps the transcription initiation site of RASGRF1, which is highly expressed in neurons and retina and has previously been implicated in retinal function and memory consolidation. Rasgrf1 −/− mice show a heavier average crystalline lens (P = 0.001). The identification of a susceptibility locus for refractive error on 15q25 will be important in characterizing the molecular mechanism responsible for the most common cause of visual impairment.</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"A genome-wide association study for myopia and refractive error identifies a susceptibility locus at 15q25","attachmentId":44118615,"attachmentType":"pdf","work_url":"https://www.academia.edu/14485103/A_genome_wide_association_study_for_myopia_and_refractive_error_identifies_a_susceptibility_locus_at_15q25","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/14485103/A_genome_wide_association_study_for_myopia_and_refractive_error_identifies_a_susceptibility_locus_at_15q25"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="5" data-entity-id="14558871" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/14558871/Genomewide_Linkage_Scans_for_Ocular_Refraction_and_Meta_analysis_of_Four_Populations_in_the_Myopia_Family_Study">Genomewide Linkage Scans for Ocular Refraction and Meta-analysis of Four Populations in the Myopia Family Study</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="33522260" href="https://independent.academia.edu/EliseCiner">Elise Ciner</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Investigative Ophthalmology & Visual Science, 2009</p><p class="ds-related-work--abstract ds2-5-body-sm">PURPOSE-Genomewide linkage scans were performed in Caucasian (CAUC) and Old Order Amish (OOA) families to identify genomic regions containing genes responsible for refractive error control. We also performed a meta-analysis by combining these results with our previous linkage results from Ashkenazi Jewish (ASHK) and African American (AFRAM) families.</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Genomewide Linkage Scans for Ocular Refraction and Meta-analysis of Four Populations in the Myopia Family Study","attachmentId":44066764,"attachmentType":"pdf","work_url":"https://www.academia.edu/14558871/Genomewide_Linkage_Scans_for_Ocular_Refraction_and_Meta_analysis_of_Four_Populations_in_the_Myopia_Family_Study","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/14558871/Genomewide_Linkage_Scans_for_Ocular_Refraction_and_Meta_analysis_of_Four_Populations_in_the_Myopia_Family_Study"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="6" data-entity-id="94080467" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/94080467/Myopia_genetics_in_genome_wide_association_and_post_genome_wide_association_study_era">Myopia genetics in genome-wide association and post-genome-wide association study era</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="166506679" href="https://independent.academia.edu/TanQingQing">Qing-Qing Tan</a></div><p class="ds-related-work--metadata ds2-5-body-xs">International Journal of Ophthalmology, 2019</p><p class="ds-related-work--abstract ds2-5-body-sm">• Genome-wide association studies (GWAS) of myopia and refractive error have generated exciting results and identified novel risk-associated loci. However, the interpretation of the findings of GWAS of complex diseases is not straightforward and has remained challenging. This review provides a brief summary of the main focus on the advantages and limitations of GWAS of myopia, with potential strategies that may contribute to further insight into the genetics of myopia in the post-GWAS or omics era.</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Myopia genetics in genome-wide association and post-genome-wide association study era","attachmentId":96639366,"attachmentType":"pdf","work_url":"https://www.academia.edu/94080467/Myopia_genetics_in_genome_wide_association_and_post_genome_wide_association_study_era","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/94080467/Myopia_genetics_in_genome_wide_association_and_post_genome_wide_association_study_era"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="7" data-entity-id="20393150" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/20393150/Fine_mapping_linkage_analysis_identifies_a_novel_susceptibility_locus_for_myopia_on_chromosome_2q37_adjacent_to_but_not_overlapping_MYP12">Fine mapping linkage analysis identifies a novel susceptibility locus for myopia on chromosome 2q37 adjacent to but not overlapping MYP12</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="41763214" href="https://independent.academia.edu/KellyPertile">Kelly Pertile</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Molecular vision</p><p class="ds-related-work--abstract ds2-5-body-sm">Myopia (shortsightedness) is one of the most common ocular conditions worldwide and results in blurred distance vision. It is a complex trait influenced by both genetic and environmental factors. We have previously reported linkage of myopia to a 13.01 cM region of chromosome 2q37 in three large multigenerational Australian families that initially overlapped with the known myopia locus, MYP12. The purpose of this study was to perform fine mapping of this region and identify single nucleotide polymorphisms (SNPs) associated with myopia. Fine mapping linkage analysis was performed on three multigenerational families with common myopia to refine the previously mapped critical interval. SNPs in the region were also genotyped to assess for association with myopia using an independent case-control cohort. The disease interval was refined to a 1.83 cM region that is adjacent to rather than overlapping with the MYP12 locus. Subsequent sequencing of all known and hypothetical genes as well a...</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Fine mapping linkage analysis identifies a novel susceptibility locus for myopia on chromosome 2q37 adjacent to but not overlapping MYP12","attachmentId":41336110,"attachmentType":"pdf","work_url":"https://www.academia.edu/20393150/Fine_mapping_linkage_analysis_identifies_a_novel_susceptibility_locus_for_myopia_on_chromosome_2q37_adjacent_to_but_not_overlapping_MYP12","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/20393150/Fine_mapping_linkage_analysis_identifies_a_novel_susceptibility_locus_for_myopia_on_chromosome_2q37_adjacent_to_but_not_overlapping_MYP12"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="8" data-entity-id="60958484" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/60958484/Evaluation_of_12_myopia_associated_genes_in_Chinese_patients_with_high_myopia">Evaluation of 12 myopia-associated genes in Chinese patients with high myopia</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="45139348" href="https://independent.academia.edu/QingjiongZhang">Qingjiong Zhang</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Investigative ophthalmology & visual science, 2015</p><p class="ds-related-work--abstract ds2-5-body-sm">Two recent large-scale genome-wide association studies identified significant associations between myopia and SNPs near the PRSS56, BMP3, KCNQ5, LAMA2, TOX, TJP2, RDH5, ZIC2, RASGRF1, GJD2, RBFOX1, and SHISA6 genes. Our study is to examine whether rare variants in these genes contribute to high myopia. Whole exome sequencing was performed on samples of 298 probands with early-onset high myopia (spherical refraction in each meridian ≤-6.00 D in both eyes; age of onset &lt;7 years) and 195 controls (different forms of retinal degeneration including Leber congenital amaurosis, cone-rod dystrophy, and familial exudative vitroretinopathy). Potential variations in these genes were selected for further validation and comparison to the controls. Moreover, Sanger sequencing was used to evaluate the coding regions and the upstream 800 base pairs of GJD2 in 395 additional subjects with late-onset moderate to high myopia (loMHM) (spherical refraction in each meridian ≤-4.00 D; age of onset ≥7 y...</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Evaluation of 12 myopia-associated genes in Chinese patients with high myopia","attachmentId":74174947,"attachmentType":"pdf","work_url":"https://www.academia.edu/60958484/Evaluation_of_12_myopia_associated_genes_in_Chinese_patients_with_high_myopia","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/60958484/Evaluation_of_12_myopia_associated_genes_in_Chinese_patients_with_high_myopia"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="9" data-entity-id="12692223" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/12692223/Genome_wide_meta_analysis_of_myopia_and_hyperopia_provides_evidence_for_replication_of_11_loci">Genome-wide meta-analysis of myopia and hyperopia provides evidence for replication of 11 loci</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="31704058" href="https://independent.academia.edu/BenOostra">Ben Oostra</a></div><p class="ds-related-work--metadata ds2-5-body-xs">PloS one, 2014</p><p class="ds-related-work--abstract ds2-5-body-sm">Refractive error (RE) is a complex, multifactorial disorder characterized by a mismatch between the optical power of the eye and its axial length that causes object images to be focused off the retina. The two major subtypes of RE are myopia (nearsightedness) and hyperopia (farsightedness), which represent opposite ends of the distribution of the quantitative measure of spherical refraction. We performed a fixed effects meta-analysis of genome-wide association results of myopia and hyperopia from 9 studies of European-derived populations: AREDS, KORA, FES, OGP-Talana, MESA, RSI, RSII, RSIII and ERF. One genome-wide significant region was observed for myopia, corresponding to a previously identified myopia locus on 8q12 (p = 1.25×10(-8)), which has been reported by Kiefer et al. as significantly associated with myopia age at onset and Verhoeven et al. as significantly associated to mean spherical-equivalent (MSE) refractive error. We observed two genome-wide significant associations ...</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Genome-wide meta-analysis of myopia and hyperopia provides evidence for replication of 11 loci","attachmentId":46004059,"attachmentType":"pdf","work_url":"https://www.academia.edu/12692223/Genome_wide_meta_analysis_of_myopia_and_hyperopia_provides_evidence_for_replication_of_11_loci","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/12692223/Genome_wide_meta_analysis_of_myopia_and_hyperopia_provides_evidence_for_replication_of_11_loci"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div></div></div><div class="ds-sticky-ctas--wrapper js-loswp-sticky-ctas hidden"><div class="ds-sticky-ctas--grid-container"><div class="ds-sticky-ctas--container"><button class="ds2-5-button js-swp-download-button" data-signup-modal="{"location":"continue-reading-button--sticky-ctas","attachmentId":40014317,"attachmentType":"pdf","workUrl":null}">See full PDF</button><button class="ds2-5-button ds2-5-button--secondary js-swp-download-button" data-signup-modal="{"location":"download-pdf-button--sticky-ctas","attachmentId":40014317,"attachmentType":"pdf","workUrl":null}"><span class="material-symbols-outlined" style="font-size: 20px" translate="no">download</span>Download PDF</button></div></div></div><div class="ds-below-fold--grid-container"><div class="ds-work--container js-loswp-embedded-document"><div class="attachment_preview" data-attachment="Attachment_40014317" style="display: none"><div class="js-scribd-document-container"><div class="scribd--document-loading js-scribd-document-loader" style="display: block;"><img alt="Loading..." src="//a.academia-assets.com/images/loaders/paper-load.gif" /><p>Loading Preview</p></div></div><div style="text-align: center;"><div class="scribd--no-preview-alert js-preview-unavailable"><p>Sorry, preview is currently unavailable. You can download the paper by clicking the button above.</p></div></div></div></div><div class="ds-sidebar--container js-work-sidebar"><div class="ds-related-content--container"><h2 class="ds-related-content--heading">Related papers</h2><div class="ds-related-work--container js-related-work-sidebar-card" data-collection-position="0" data-entity-id="70972008" data-sort-order="default"><a class="ds-related-work--title js-related-work-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/70972008/Genes_Proteins_and_Biological_Pathways_in_Human_and_Animal_Myopia">Genes, Proteins and Biological Pathways in Human and Animal Myopia</a><div class="ds-related-work--metadata"><a class="js-related-work-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="113370058" href="https://rmit.academia.edu/LorettaVocale">Loretta Vocale</a></div><p class="ds-related-work--metadata ds2-5-body-xs">2019</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Genes, Proteins and Biological Pathways in Human and Animal Myopia","attachmentId":80503569,"attachmentType":"pdf","work_url":"https://www.academia.edu/70972008/Genes_Proteins_and_Biological_Pathways_in_Human_and_Animal_Myopia","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-related-work-grid-card-view-pdf" href="https://www.academia.edu/70972008/Genes_Proteins_and_Biological_Pathways_in_Human_and_Animal_Myopia"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-related-work-sidebar-card" data-collection-position="1" data-entity-id="115941730" data-sort-order="default"><a class="ds-related-work--title js-related-work-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/115941730/Novel_locus_for_X_linked_recessive_high_myopia_maps_to_Xq23_q25_but_outside_MYP1">Novel locus for X linked recessive high myopia maps to Xq23-q25 but outside MYP1</a><div class="ds-related-work--metadata"><a class="js-related-work-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="45139348" href="https://independent.academia.edu/QingjiongZhang">Qingjiong Zhang</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Journal of Medical Genetics, 2005</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Novel locus for X linked recessive high myopia maps to Xq23-q25 but outside MYP1","attachmentId":112208797,"attachmentType":"pdf","work_url":"https://www.academia.edu/115941730/Novel_locus_for_X_linked_recessive_high_myopia_maps_to_Xq23_q25_but_outside_MYP1","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-related-work-grid-card-view-pdf" href="https://www.academia.edu/115941730/Novel_locus_for_X_linked_recessive_high_myopia_maps_to_Xq23_q25_but_outside_MYP1"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-related-work-sidebar-card" data-collection-position="2" data-entity-id="30599836" data-sort-order="default"><a class="ds-related-work--title js-related-work-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/30599836/Large_scale_international_replication_and_meta_analysis_study_confirms_association_of_the_15q14_locus_with_myopia_The_CREAM_consortium">Large scale international replication and meta-analysis study confirms association of the 15q14 locus with myopia. The CREAM consortium</a><div class="ds-related-work--metadata"><a class="js-related-work-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="58305271" href="https://independent.academia.edu/VVerhoeven">Virginie Verhoeven</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Human Genetics, 2012</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Large scale international replication and meta-analysis study confirms association of the 15q14 locus with myopia. 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data-sort-order="default"><a class="ds-related-work--title js-related-work-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/20393141/Linkage_Replication_of_the_MYP12_Locus_in_Common_Myopia">Linkage Replication of the MYP12 Locus in Common Myopia</a><div class="ds-related-work--metadata"><a class="js-related-work-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="41763214" href="https://independent.academia.edu/KellyPertile">Kelly Pertile</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Investigative Ophthalmology &amp; Visual Science, 2007</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Linkage Replication of the MYP12 Locus in Common 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