Genome-Wide Analysis Points to Roles for Extracellular Matrix Remodeling, the Visual Cycle, and Neuronal Development in Myopia
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{"title"=>"Genome-Wide Analysis Points to Roles for Extracellular Matrix Remodeling, the Visual Cycle, and Neuronal Development in Myopia", "type"=>"journal", "authors"=>[{"first_name"=>"Amy K.", "last_name"=>"Kiefer", "scopus_author_id"=>"43861423500"}, {"first_name"=>"Joyce Y.", "last_name"=>"Tung", "scopus_author_id"=>"36852202500"}, {"first_name"=>"Chuong B.", "last_name"=>"Do", "scopus_author_id"=>"42061293600"}, {"first_name"=>"David A.", "last_name"=>"Hinds", "scopus_author_id"=>"16739450500"}, {"first_name"=>"Joanna L.", "last_name"=>"Mountain", "scopus_author_id"=>"7005346177"}, {"first_name"=>"Uta", "last_name"=>"Francke", "scopus_author_id"=>"7202766169"}, {"first_name"=>"Nicholas", "last_name"=>"Eriksson", "scopus_author_id"=>"24343781500"}], "year"=>2013, "source"=>"PLoS Genetics", "identifiers"=>{"issn"=>"15537390", "arxiv"=>"arXiv:1209.2089v1", "scopus"=>"2-s2.0-84874777264", "sgr"=>"84874777264", "pui"=>"368490531", "isbn"=>"1553-7404 (Electronic)\\r1553-7390 (Linking)", "pmid"=>"23468642", "doi"=>"10.1371/journal.pgen.1003299"}, "id"=>"cef3af42-8a63-320a-ad3f-4b8330ae4b6a", "abstract"=>"Myopia, or nearsightedness, is the most common eye disorder, resulting primarily from excess elongation of the eye. The etiology of myopia, although known to be complex, is poorly understood. Here we report the largest ever genome-wide association study (45,771 participants) on myopia in Europeans. We performed a survival analysis on age of myopia onset and identified 22 significant associations ([Formula: see text]), two of which are replications of earlier associations with refractive error. Ten of the 20 novel associations identified replicate in a separate cohort of 8,323 participants who reported if they had developed myopia before age 10. These 22 associations in total explain 2.9% of the variance in myopia age of onset and point toward a number of different mechanisms behind the development of myopia. One association is in the gene PRSS56, which has previously been linked to abnormally small eyes; one is in a gene that forms part of the extracellular matrix (LAMA2); two are in or near genes involved in the regeneration of 11-cis-retinal (RGR and RDH5); two are near genes known to be involved in the growth and guidance of retinal ganglion cells (ZIC2, SFRP1); and five are in or near genes involved in neuronal signaling or development. These novel findings point toward multiple genetic factors involved in the development of myopia and suggest that complex interactions between extracellular matrix remodeling, neuronal development, and visual signals from the retina may underlie the development of myopia in humans.", "link"=>"http://www.mendeley.com/research/genomewide-analysis-points-roles-extracellular-matrix-remodeling-visual-cycle-neuronal-development-m", "reader_count"=>72, "reader_count_by_academic_status"=>{"Unspecified"=>5, "Professor > Associate Professor"=>3, "Researcher"=>16, "Student > Doctoral Student"=>7, "Student > Ph. D. Student"=>17, "Student > Postgraduate"=>3, "Student > Master"=>6, "Other"=>6, "Student > Bachelor"=>5, "Lecturer > Senior Lecturer"=>1, "Professor"=>3}, "reader_count_by_user_role"=>{"Unspecified"=>5, "Professor > Associate Professor"=>3, "Researcher"=>16, "Student > Doctoral Student"=>7, "Student > Ph. D. Student"=>17, "Student > Postgraduate"=>3, "Student > Master"=>6, "Other"=>6, "Student > Bachelor"=>5, "Lecturer > Senior Lecturer"=>1, "Professor"=>3}, "reader_count_by_subject_area"=>{"Unspecified"=>8, "Biochemistry, Genetics and Molecular Biology"=>9, "Mathematics"=>2, "Medicine and Dentistry"=>29, "Agricultural and Biological Sciences"=>18, "Physics and Astronomy"=>3, "Social Sciences"=>3}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>29}, "Social Sciences"=>{"Social Sciences"=>3}, "Physics and Astronomy"=>{"Physics and Astronomy"=>3}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>18}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>9}, "Mathematics"=>{"Mathematics"=>2}, "Unspecified"=>{"Unspecified"=>8}}, "reader_count_by_country"=>{"Belgium"=>1, "United States"=>1, "United Kingdom"=>1, "Australia"=>1}, "group_count"=>4}

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Figshare

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  • {"files"=>["https://ndownloader.figshare.com/files/972951"], "description"=>"<p>Regions are named with their postulated candidate gene or genes. -values under have been cut off (only the <i>LAMA2</i> and <i>LRRC4C</i> regions are affected). See <a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003299#pgen.1003299.s001\" target=\"_blank\">Figure S1</a> for plots in each region with a significant association.</p>", "links"=>[], "tags"=>["genome"], "article_id"=>641483, "categories"=>["Genetics", "Medicine"], "users"=>["Amy K. Kiefer", "Joyce Y. Tung", "Chuong B. Do", "David A. Hinds", "Joanna L. Mountain", "Uta Francke", "Nicholas Eriksson"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1003299.g001", "stats"=>{"downloads"=>3, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Negative_values_genome_wide_for_myopia_/641483", "title"=>"Negative -values genome wide for myopia.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-03-01 09:43:18"}
  • {"files"=>["https://ndownloader.figshare.com/files/1005737"], "description"=>"<p>Sex, current age, and age of onset for discovery and replication cohorts.</p>", "links"=>[], "tags"=>["genetics and genomics", "ophthalmology"], "article_id"=>666361, "categories"=>["Genetics", "Medicine"], "users"=>["Amy K. Kiefer", "Joyce Y. Tung", "Chuong B. Do", "David A. Hinds", "Joanna L. Mountain", "Uta Francke", "Nicholas Eriksson"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1003299.t001", "stats"=>{"downloads"=>0, "page_views"=>11, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Cohort_statistics_/666361", "title"=>"Cohort statistics.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-02-28 01:46:01"}
  • {"files"=>["https://ndownloader.figshare.com/files/1005717"], "description"=>"<p>Index SNPs for regions with (-corrected) -values under . Positions and alleles are given relative to the positive strand of build 37 of the human genome; alleles are listed as major/minor. The listed genes are the postulated candidate gene in each region. is the estimated imputation accuracy; HR is the hazard ratio per copy of the minor allele; -value is the -value in the discovery cohort; is the -value in the replication cohort. Significant replication -values are bolded.</p>", "links"=>[], "tags"=>["snps", "regions"], "article_id"=>666341, "categories"=>["Genetics", "Medicine"], "users"=>["Amy K. Kiefer", "Joyce Y. Tung", "Chuong B. Do", "David A. Hinds", "Joanna L. Mountain", "Uta Francke", "Nicholas Eriksson"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1003299.t002", "stats"=>{"downloads"=>0, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Index_SNPs_for_regions_with_/666341", "title"=>"Index SNPs for regions with .", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-02-28 01:45:41"}
  • {"files"=>["https://ndownloader.figshare.com/files/972955"], "description"=>"<p>The genetic propensity score is computed as the number of risk alleles across the 22 genome-wide significant SNPs. Curves show estimated survival probability (i.e., the probability of not having developed myopia) by age under the fitted Cox model for the 10th, 50th, and 90th percentiles of scores (15.01, 18.46, and 21.95, respectively).</p>", "links"=>[], "tags"=>["curves", "propensity"], "article_id"=>641487, "categories"=>["Genetics", "Medicine"], "users"=>["Amy K. Kiefer", "Joyce Y. Tung", "Chuong B. Do", "David A. Hinds", "Joanna L. Mountain", "Uta Francke", "Nicholas Eriksson"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1003299.g002", "stats"=>{"downloads"=>1, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Estimated_survival_curves_by_genetic_propensity_score_/641487", "title"=>"Estimated survival curves by genetic propensity score.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-03-01 09:43:46"}

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