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(PDF) The association between L:M cone ratio, cone opsin genes and myopia susceptibility
<!DOCTYPE html> <html > <head> <meta charset="utf-8"> <meta rel="search" type="application/opensearchdescription+xml" href="/open_search.xml" title="Academia.edu"> <meta content="width=device-width, initial-scale=1" name="viewport"> <meta name="google-site-verification" content="bKJMBZA7E43xhDOopFZkssMMkBRjvYERV-NaN4R6mrs"> <meta name="csrf-param" content="authenticity_token" /> <meta name="csrf-token" content="xIGQV_WrS7ZmmlseG6e6phbOtqVjNlH_K1KmLIkYbykz5qABZW6PUw-0OfPJf34SbKA_7TLnWWxatiuSztvbYw" /> <meta name="citation_title" content="The association between L:M cone ratio, cone opsin genes and myopia susceptibility" /> <meta name="citation_journal_title" content="Vision Research" /> <meta name="citation_author" content="Jay Neitz" /> <meta name="twitter:card" content="summary" /> <meta name="twitter:url" content="https://www.academia.edu/64588839/The_association_between_L_M_cone_ratio_cone_opsin_genes_and_myopia_susceptibility" /> <meta name="twitter:title" content="The association between L:M cone ratio, cone opsin genes and myopia susceptibility" /> <meta name="twitter:description" content="In syndromic forms of myopia caused by long (L) to middle (M) wavelength (L/M) interchange mutations, erroneous contrast signals from ON-bipolar cells activated by cones with different levels of opsin expression are suggested to make the eye" /> <meta name="twitter:image" content="https://0.academia-photos.com/38795542/10751984/12002008/s200_jay.neitz.jpg" /> <meta property="fb:app_id" content="2369844204" /> <meta property="og:type" content="article" /> <meta property="og:url" content="https://www.academia.edu/64588839/The_association_between_L_M_cone_ratio_cone_opsin_genes_and_myopia_susceptibility" /> <meta property="og:title" content="The association between L:M cone ratio, cone opsin genes and myopia susceptibility" /> <meta property="og:image" content="http://a.academia-assets.com/images/open-graph-icons/fb-paper.gif" /> <meta property="og:description" content="In syndromic forms of myopia caused by long (L) to middle (M) wavelength (L/M) interchange mutations, erroneous contrast signals from ON-bipolar cells activated by cones with different levels of opsin expression are suggested to make the eye" /> <meta property="article:author" content="https://washington.academia.edu/JayNeitz" /> <meta name="description" content="In syndromic forms of myopia caused by long (L) to middle (M) wavelength (L/M) interchange mutations, erroneous contrast signals from ON-bipolar cells activated by cones with different levels of opsin expression are suggested to make the eye" /> <title>(PDF) The association between L:M cone ratio, cone opsin genes and myopia susceptibility</title> <link rel="canonical" href="https://www.academia.edu/64588839/The_association_between_L_M_cone_ratio_cone_opsin_genes_and_myopia_susceptibility" /> <script async src="https://www.googletagmanager.com/gtag/js?id=G-5VKX33P2DS"></script> <script> window.dataLayer = window.dataLayer || []; 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window.loswp.work = {"work":{"id":64588839,"created_at":"2021-12-16T09:46:09.210-08:00","from_world_paper_id":187474883,"updated_at":"2024-12-22T23:36:01.922-08:00","_data":{"publisher":"Elsevier BV","grobid_abstract":"In syndromic forms of myopia caused by long (L) to middle (M) wavelength (L/M) interchange mutations, erroneous contrast signals from ON-bipolar cells activated by cones with different levels of opsin expression are suggested to make the eye susceptible to increased growth. This susceptibility is modulated by the L:M cone ratio. Here, we examined L and M opsin genes, L:M cone ratios and their association with common refractive errors in a population with low myopia prevalence. Cycloplegic autorefraction and ocular biometry were obtained for Norwegian genetically-confirmed normal trichromats. L:M cone ratios were estimated from spectral sensitivity functions measured with full-field ERG, after adjusting for individual differences in the wavelength of peak absorption deduced from cone opsin genetics. Mean L:M cone ratios and the frequency of alanine at L opsin position 180 were higher in males than what has been reported in males in populations with high myopia prevalence. High L:M cone ratios in females were associated with lower degree of myopia, and myopia was more frequent in females who were heterozygous for L opsin exon 3 haplotypes than in those who were homozygous. The results suggest that the L:M cone ratio, combined with milder versions of L opsin gene polymorphisms, may play a role in common myopia. This may in part explain the low myopia prevalence in Norwegian adolescents and why myopia prevalence was higher in females who were heterozygous for the L opsin exon 3 haplotype, since females are twice as likely to have genetic polymorphisms carried on the X-chromosome.","publication_name":"Vision Research","grobid_abstract_attachment_id":"76556055"},"document_type":"paper","pre_hit_view_count_baseline":null,"quality":"high","language":"en","title":"The association between L:M cone ratio, cone opsin genes and myopia susceptibility","broadcastable":true,"draft":null,"has_indexable_attachment":true,"indexable":true}}["work"]; window.loswp.workCoauthors = [38795542]; 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":76556055,"attachmentType":"pdf"}"><img alt="First page of “The association between L:M cone ratio, cone opsin genes and myopia susceptibility”" class="ds-work-cover--cover-thumbnail" src="https://0.academia-photos.com/attachment_thumbnails/76556055/mini_magick20211216-11382-1dzexn2.png?1639680018" /><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">The association between L:M cone ratio, cone opsin genes and myopia susceptibility</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="38795542" href="https://washington.academia.edu/JayNeitz"><img alt="Profile image of Jay Neitz" class="ds-work-card--author-avatar" src="https://0.academia-photos.com/38795542/10751984/12002008/s65_jay.neitz.jpg" />Jay Neitz</a></div><div class="ds-work-card--detail"><p class="ds-work-card--detail ds2-5-body-sm">Vision Research</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">9 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 = 64588839; 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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">In syndromic forms of myopia caused by long (L) to middle (M) wavelength (L/M) interchange mutations, erroneous contrast signals from ON-bipolar cells activated by cones with different levels of opsin expression are suggested to make the eye susceptible to increased growth. This susceptibility is modulated by the L:M cone ratio. Here, we examined L and M opsin genes, L:M cone ratios and their association with common refractive errors in a population with low myopia prevalence. Cycloplegic autorefraction and ocular biometry were obtained for Norwegian genetically-confirmed normal trichromats. L:M cone ratios were estimated from spectral sensitivity functions measured with full-field ERG, after adjusting for individual differences in the wavelength of peak absorption deduced from cone opsin genetics. Mean L:M cone ratios and the frequency of alanine at L opsin position 180 were higher in males than what has been reported in males in populations with high myopia prevalence. High L:M cone ratios in females were associated with lower degree of myopia, and myopia was more frequent in females who were heterozygous for L opsin exon 3 haplotypes than in those who were homozygous. The results suggest that the L:M cone ratio, combined with milder versions of L opsin gene polymorphisms, may play a role in common myopia. This may in part explain the low myopia prevalence in Norwegian adolescents and why myopia prevalence was higher in females who were heterozygous for the L opsin exon 3 haplotype, since females are twice as likely to have genetic polymorphisms carried on the X-chromosome.</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":76556055,"attachmentType":"pdf","workUrl":"https://www.academia.edu/64588839/The_association_between_L_M_cone_ratio_cone_opsin_genes_and_myopia_susceptibility"}">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":76556055,"attachmentType":"pdf","workUrl":"https://www.academia.edu/64588839/The_association_between_L_M_cone_ratio_cone_opsin_genes_and_myopia_susceptibility"}"><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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Comparison of genetic risks between children and adults</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="32558522" href="https://independent.academia.edu/CarolineKlaver">Caroline Klaver</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Genetic epidemiology, 2016</p><p class="ds-related-work--abstract ds2-5-body-sm">Previous studies have identified many genetic loci for refractive error and myopia. We aimed to investigate the effect of these loci on ocular biometry as a function of age in children, adolescents, and adults. The study population consisted of three age groups identified from the international CREAM consortium: 5,490 individuals aged &lt;10 years; 5,000 aged 10-25 years; and 16,274 aged &gt;25 years. All participants had undergone standard ophthalmic examination including measurements of axial length (AL) and corneal radius (CR). We examined the lead SNP at all 39 currently known genetic loci for refractive error identified from genome-wide association studies (GWAS), as well as a combined genetic risk score (GRS). The beta coefficient for association between SNP genotype or GRS versus AL/CR was compared across the three age groups, adjusting for age, sex, and principal components. Analyses were Bonferroni-corrected. In the age group &lt;10 years, three loci (GJD2, CHRNG, ZIC2) wer...</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":"When do myopia genes have their effect? Comparison of genetic risks between children and adults","attachmentId":105645311,"attachmentType":"pdf","work_url":"https://www.academia.edu/106451236/When_do_myopia_genes_have_their_effect_Comparison_of_genetic_risks_between_children_and_adults","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/106451236/When_do_myopia_genes_have_their_effect_Comparison_of_genetic_risks_between_children_and_adults"><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="14558879" 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/14558879/Candidate_high_myopia_loci_on_chromosomes_18p_and_12q_do_not_play_a_major_role_in_susceptibility_to_common_myopia">Candidate high myopia loci on chromosomes 18p and 12q do not play a major role in susceptibility to common 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="33522260" href="https://independent.academia.edu/EliseCiner">Elise Ciner</a></div><p class="ds-related-work--metadata ds2-5-body-xs">BMC medical genetics, 2004</p><p class="ds-related-work--abstract ds2-5-body-sm">To determine whether previously reported loci predisposing to nonsyndromic high myopia show linkage to common myopia in pedigrees from two ethnic groups: Ashkenazi Jewish and Amish. We hypothesized that these high myopia loci might exhibit allelic heterogeneity and be responsible for moderate /mild or common myopia. Cycloplegic and manifest refraction were performed on 38 Jewish and 40 Amish families. Individuals with at least -1.00 D in each meridian of both eyes were classified as myopic. Genomic DNA was genotyped with 12 markers on chromosomes 12q21-23 and 18p11.3. Parametric and nonparametric linkage analyses were conducted to determine whether susceptibility alleles at these loci are important in families with less severe, clinical forms of myopia. There was no strong evidence of linkage of common myopia to these candidate regions: all two-point and multipoint heterogeneity LOD scores were &lt; 1.0 and non-parametric linkage p-values were &gt; 0.01. However, one Amish family sh...</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":"Candidate high myopia loci on chromosomes 18p and 12q do not play a major role in susceptibility to common myopia","attachmentId":44066761,"attachmentType":"pdf","work_url":"https://www.academia.edu/14558879/Candidate_high_myopia_loci_on_chromosomes_18p_and_12q_do_not_play_a_major_role_in_susceptibility_to_common_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/14558879/Candidate_high_myopia_loci_on_chromosomes_18p_and_12q_do_not_play_a_major_role_in_susceptibility_to_common_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="2" data-entity-id="61352947" 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/61352947/Common_Variant_in_Myocilin_Gene_Is_Associated_with_High_Myopia_in_Isolated_Population_of_Kor%C4%8Dula_Island_Croatia">Common Variant in Myocilin Gene Is Associated with High Myopia in Isolated Population of Korčula Island, Croatia</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="65813977" href="https://independent.academia.edu/JasnaPavi%C4%8Di%C4%87Astalo%C5%A1">Jasna Pavičić-Astaloš</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Croat Med J, 2009</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":"Common Variant in Myocilin Gene Is Associated with High Myopia in Isolated Population of Korčula Island, Croatia","attachmentId":74407859,"attachmentType":"pdf","work_url":"https://www.academia.edu/61352947/Common_Variant_in_Myocilin_Gene_Is_Associated_with_High_Myopia_in_Isolated_Population_of_Kor%C4%8Dula_Island_Croatia","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/61352947/Common_Variant_in_Myocilin_Gene_Is_Associated_with_High_Myopia_in_Isolated_Population_of_Kor%C4%8Dula_Island_Croatia"><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="96715802" 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/96715802/Genetic_Variants_Associated_With_Human_Eye_Size_Are_Distinct_From_Those_Conferring_Susceptibility_to_Myopia">Genetic Variants Associated With Human Eye Size Are Distinct From Those Conferring Susceptibility to 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="151975719" href="https://ustc.academia.edu/jiangtiancui">jiangtian cui</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Investigative Opthalmology &amp; Visual Science, 2021</p><p class="ds-related-work--abstract ds2-5-body-sm">PURPOSE. Emmetropization requires coordinated scaling of the major ocular components, corneal curvature and axial length. This coordination is achieved in part through a shared set of genetic variants that regulate eye size. Poorly coordinated scaling of corneal curvature and axial length results in refractive error. We tested the hypothesis that genetic variants regulating eye size in emmetropic eyes are distinct from those conferring susceptibility to refractive error. METHODS. A genome-wide association study (GWAS) for corneal curvature in 22,180 adult emmetropic individuals was performed as a proxy for a GWAS for eye size. A polygenic score created using lead GWAS variants was tested for association with corneal curvature and axial length in an independent sample: 437 classified as emmetropic and 637 as ametropic. The genetic correlation between eye size and refractive error was calculated using linkage disequilibrium score regression for approximately 1 million genetic variants. RESULTS. The GWAS for corneal curvature in emmetropes identified 32 independent genetic variants (P < 5.0e-08). A polygenic score created using these 32 genetic markers explained 3.5% (P < 0.001) and 2.0% (P = 0.001) of the variance in corneal curvature and axial length, respectively, in the independent sample of emmetropic individuals but was not predictive of these traits in ametropic individuals. The genetic correlation between eye size and refractive error was close to zero (r g = 0.00; SE = 0.06; P = 0.95). CONCLUSIONS. These results support the hypothesis that genetic variants regulating eye size in emmetropic eyes do not overlap with those conferring susceptibility to myopia. This suggests that distinct biological pathways regulate normal eye growth and myopia development.</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":"Genetic Variants Associated With Human Eye Size Are Distinct From Those Conferring Susceptibility to Myopia","attachmentId":98537141,"attachmentType":"pdf","work_url":"https://www.academia.edu/96715802/Genetic_Variants_Associated_With_Human_Eye_Size_Are_Distinct_From_Those_Conferring_Susceptibility_to_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/96715802/Genetic_Variants_Associated_With_Human_Eye_Size_Are_Distinct_From_Those_Conferring_Susceptibility_to_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="4" data-entity-id="91289890" 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/91289890/Linkage_Analysis_of_the_Genetic_Loci_for_High_Myopia_on_18p_12q_and_17q_in_51_U_K_Families">Linkage Analysis of the Genetic Loci for High Myopia on 18p, 12q, and 17q in 51 U.K. Families</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="41279002" href="https://independent.academia.edu/RicardoPongWong">Ricardo PongWong</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Investigative Opthalmology &amp; Visual Science, 2004</p><p class="ds-related-work--abstract ds2-5-body-sm">PURPOSE. To determine the extent to which high myopia in a cohort of 51 U.K. families can be attributed to currently identified genetic loci. METHODS. The families comprised 245 subjects with phenotypic information and DNA available, of whom 170 were classified as affected. Subjects were genotyped for microsatellite markers spanning ϳ40cM regions on 18p (MYP2), 12q (MYP3) and 17q, together with markers flanking COL2A1, COL11A1, and FBN1. Two-point linkage analyses were performed using the same disease gene segregation model as was used in the original publications, followed by nonparametric and multipoint analyses using Genehunter (http://linkage.rockefeller. edu/soft/gh/ provided in the public domain by Rockefeller University, New York, NY), with additional maximization over the parameter ␣, the proportion of linked families. RESULTS. Evidence of linkage was found for the MYP3 locus on 12q (two-point Z max ϭ 2.54, P ϭ 0.0003 and multipoint hLOD ϭ 1.08 at ␣ ϭ 0.24, P ϭ 0.023 for marker D12S332; nonparametric linkage [NPL] ϭ 1.49, P ϭ 0.07 for marker D12S1607). For the 17q locus there was weak evidence of excess allele sharing and linkage under a recessive model (NPL ϭ 1.34, P ϭ 0.09 for marker D17S956; two-point hLOD ϭ 1.24 at ␣ ϭ 0.30 for marker D17S1795; multipoint hLOD ϭ 1.24 at ␣ ϭ 0.17, P ϭ 0.014 for marker at 77.68 cM, between markers D17S956 and D17S1853). No significant linkage was found to the MYP2 locus on 18p, or to the COL2A1, COL11A1, and FBN1 genes. CONCLUSIONS. These results suggest that the MYP3 locus on 12q could be responsible for high myopia in approximately 25% of the U.K. families showing apparent autosomal dominant transmission, but that the loci on 18p and 17q are less common causes. Thus, additional loci for high myopia are likely to be the cause of the majority of cases of high myopia in the United Kingdom.</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 Analysis of the Genetic Loci for High Myopia on 18p, 12q, and 17q in 51 U.K. Families","attachmentId":94618499,"attachmentType":"pdf","work_url":"https://www.academia.edu/91289890/Linkage_Analysis_of_the_Genetic_Loci_for_High_Myopia_on_18p_12q_and_17q_in_51_U_K_Families","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/91289890/Linkage_Analysis_of_the_Genetic_Loci_for_High_Myopia_on_18p_12q_and_17q_in_51_U_K_Families"><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="20393142" 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/20393142/Genetic_Mapping_of_Myopia_Susceptibility_Loci">Genetic Mapping of Myopia Susceptibility 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="41763214" href="https://independent.academia.edu/KellyPertile">Kelly Pertile</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Investigative Ophthalmology & Visual Science, 2007</p><p class="ds-related-work--abstract ds2-5-body-sm">PURPOSE. Myopia (short sightedness) is a complex trait influenced by as yet unidentified genetic factors. To date, there have been four myopia susceptibility loci (MYP7 to -10) identified in twin studies, but these are yet to be independently verified. In an independent yet ethnically and phenotypically similar twin cohort, linkage to these chromosomal regions was sought. METHODS. Participants were 223 dizygotic twin pairs from the Australian Twin Registry who were assessed for evidence of linkage, by using polymorphic microsatellite markers spanning MYP7-10. Data were analyzed by using Haseman-Elston regression analysis.</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":"Genetic Mapping of Myopia Susceptibility Loci","attachmentId":41336113,"attachmentType":"pdf","work_url":"https://www.academia.edu/20393142/Genetic_Mapping_of_Myopia_Susceptibility_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/20393142/Genetic_Mapping_of_Myopia_Susceptibility_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 class="ds-related-work--container js-wsj-grid-card" data-collection-position="6" 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="7" 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="8" data-entity-id="30599836" 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/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-wsj-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. The CREAM consortium","attachmentId":51042841,"attachmentType":"pdf","work_url":"https://www.academia.edu/30599836/Large_scale_international_replication_and_meta_analysis_study_confirms_association_of_the_15q14_locus_with_myopia_The_CREAM_consortium","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/30599836/Large_scale_international_replication_and_meta_analysis_study_confirms_association_of_the_15q14_locus_with_myopia_The_CREAM_consortium"><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="10521098" 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/10521098/Heritability_of_Refractive_Error_and_Ocular_Biometrics_The_Genes_in_Myopia_GEM_Twin_Study">Heritability of Refractive Error and Ocular Biometrics: The Genes in Myopia (GEM) Twin 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="25787206" href="https://independent.academia.edu/ChristineChen12">Christine Chen</a></div><p class="ds-related-work--metadata ds2-5-body-xs">2006</p><p class="ds-related-work--abstract ds2-5-body-sm">A classic twin study was undertaken to assess the contribution of genes and environment to the development of refractive errors and ocular biometrics in a twin population. METHODS. A total of 1224 twins (345 monozygotic [MZ] and 267 dizygotic [DZ] twin pairs) aged between 18 and 88 years were examined. All twins completed a questionnaire consisting of a medical history, education, and zygosity. Objective refraction was measured in all twins, and biometric measurements were obtained using partial coherence interferometry. RESULTS. Intrapair correlations for spherical equivalent and ocular biometrics were significantly higher in the MZ than in the DZ twin pairs (P Ͻ 0.05), when refraction was considered as a continuous variable. A significant gender difference in the variation of spherical equivalent and ocular biometrics was found (P Ͻ 0.05). A genetic model specifying an additive, dominant, and unique environmental factor that was sex limited was the best fit for all measured variables. Heritability of spherical equivalents of 88% and 75% were found in the men and women, respectively, whereas, that of axial length was 94% and 92%, respectively. Additive genetic effects accounted for a greater proportion of the variance in spherical equivalent, whereas the variance in ocular biometrics, particularly axial length was explained mostly by dominant genetic effects. CONCLUSIONS. Genetic factors, both additive and dominant, play a significant role in refractive error (myopia and hypermetropia) as well as in ocular biometrics, particularly axial length. The sex limitation ADE model (additive genetic, nonadditive genetic, and environmental components) provided the best-fit genetic model for all parameters. (Invest Ophthalmol Vis Sci. 2006;47:4756 -4761)</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":"Heritability of Refractive Error and Ocular Biometrics: The Genes in Myopia (GEM) Twin Study","attachmentId":36519333,"attachmentType":"pdf","work_url":"https://www.academia.edu/10521098/Heritability_of_Refractive_Error_and_Ocular_Biometrics_The_Genes_in_Myopia_GEM_Twin_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/10521098/Heritability_of_Refractive_Error_and_Ocular_Biometrics_The_Genes_in_Myopia_GEM_Twin_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></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":76556055,"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":76556055,"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_76556055" 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. 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class="ds-related-work--container js-related-work-sidebar-card" data-collection-position="4" data-entity-id="20631038" 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/20631038/Myocilin_polymorphisms_and_high_myopia_in_subjects_of_European_origin">Myocilin polymorphisms and high myopia in subjects of European origin</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="32492400" href="https://bristol.academia.edu/GeorgeMcMahon">George McMahon</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Molecular vision, 2009</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":"Myocilin polymorphisms and high myopia in subjects of European 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href="https://www.academia.edu/81497055/Focusing_In_on_the_Complex_Genetics_of_Myopia">Focusing In on the Complex Genetics of 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="58369255" href="https://independent.academia.edu/RobertWojciechowski1">Robert Wojciechowski</a></div><p class="ds-related-work--metadata ds2-5-body-xs">PLoS Genetics, 2013</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":"Focusing In on the Complex Genetics of Myopia","attachmentId":87520368,"attachmentType":"pdf","work_url":"https://www.academia.edu/81497055/Focusing_In_on_the_Complex_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 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ds2-5-body-xs">PLOS 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":"Genetic Variants on Chromosome 1q41 Influence Ocular Axial Length and High Myopia","attachmentId":49223394,"attachmentType":"pdf","work_url":"https://www.academia.edu/5600260/Genetic_Variants_on_Chromosome_1q41_Influence_Ocular_Axial_Length_and_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-related-work-grid-card-view-pdf" href="https://www.academia.edu/5600260/Genetic_Variants_on_Chromosome_1q41_Influence_Ocular_Axial_Length_and_High_Myopia"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" 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and<i>HGF</i>Genes</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">Investigative Ophthalmology & Visual Science, 2009</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":"High Myopia Is Not Associated with the SNPs in the\u003ci\u003eTGIF\u003c/i\u003e, Lumican,\u003ci\u003eTGFB1\u003c/i\u003e, and\u003ci\u003eHGF\u003c/i\u003eGenes","attachmentId":120028306,"attachmentType":"pdf","work_url":"https://www.academia.edu/126098730/High_Myopia_Is_Not_Associated_with_the_SNPs_in_the_i_TGIF_i_Lumican_i_TGFB1_i_and_i_HGF_i_Genes","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" 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data-author-id="33522260" href="https://independent.academia.edu/EliseCiner">Elise Ciner</a></div><p class="ds-related-work--metadata ds2-5-body-xs">American Journal of Ophthalmology, 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":"Genome-wide Scan for Myopia in the Old Order Amish","attachmentId":44066772,"attachmentType":"pdf","work_url":"https://www.academia.edu/14558867/Genome_wide_Scan_for_Myopia_in_the_Old_Order_Amish","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/14558867/Genome_wide_Scan_for_Myopia_in_the_Old_Order_Amish"><span class="ds2-5-text-link__content">View 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