Genome-Wide Meta-Analysis of Myopia and Hyperopia Provides Evidence for Replication of 11 Loci
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{"title"=>"Genome-wide meta-analysis of myopia and hyperopia provides evidence for replication of 11 loci", "type"=>"journal", "authors"=>[{"first_name"=>"Claire L.", "last_name"=>"Simpson", "scopus_author_id"=>"12789397500"}, {"first_name"=>"Robert", "last_name"=>"Wojciechowski", "scopus_author_id"=>"7004317733"}, {"first_name"=>"Konrad", "last_name"=>"Oexle", "scopus_author_id"=>"57189356630"}, {"first_name"=>"Federico", "last_name"=>"Murgia", "scopus_author_id"=>"36731434300"}, {"first_name"=>"Laura", "last_name"=>"Portas", "scopus_author_id"=>"36599153800"}, {"first_name"=>"Xiaohui", "last_name"=>"Li", "scopus_author_id"=>"57008602700"}, {"first_name"=>"J. M.Verhoeven", "last_name"=>"Virginie", "scopus_author_id"=>"56364674200"}, {"first_name"=>"Veronique", "last_name"=>"Vitart", "scopus_author_id"=>"56920729200"}, {"first_name"=>"Maria", "last_name"=>"Schache", "scopus_author_id"=>"23475010700"}, {"first_name"=>"S.", "last_name"=>"Mohsen Hosseini", "scopus_author_id"=>"35797283800"}, {"first_name"=>"Pirro G.", "last_name"=>"Hysi", "scopus_author_id"=>"18133899000"}, {"first_name"=>"Leslie J.", "last_name"=>"Raffel", "scopus_author_id"=>"57195139446"}, {"first_name"=>"Mary Frances", "last_name"=>"Cotch", "scopus_author_id"=>"56823700100"}, {"first_name"=>"Emily", "last_name"=>"Chew", "scopus_author_id"=>"7102013764"}, {"first_name"=>"Barbara E.K.", "last_name"=>"Klein", "scopus_author_id"=>"55763794605"}, {"first_name"=>"Ronald", "last_name"=>"Klein", "scopus_author_id"=>"55574240992"}, {"first_name"=>"Tien Yin", "last_name"=>"Wong", "scopus_author_id"=>"35231271400"}, {"first_name"=>"Cornelia M.", "last_name"=>"Van Duijn", "scopus_author_id"=>"36037246700"}, {"first_name"=>"Paul", "last_name"=>"Mitchell", "scopus_author_id"=>"7402933815"}, {"first_name"=>"Seang Mei", "last_name"=>"Saw", "scopus_author_id"=>"7006402006"}, {"first_name"=>"Maurizio", "last_name"=>"Fossarello", "scopus_author_id"=>"6701406633"}, {"first_name"=>"Jie Jin", "last_name"=>"Wang", "scopus_author_id"=>"55664024800"}, {"first_name"=>"Ozren", "last_name"=>"Polašek", "scopus_author_id"=>"8232027400"}, {"first_name"=>"Harry", "last_name"=>"Campbell", "scopus_author_id"=>"7202318417"}, {"first_name"=>"Igor", "last_name"=>"Rudan", "scopus_author_id"=>"7007138278"}, {"first_name"=>"Ben A.", "last_name"=>"Oostra", "scopus_author_id"=>"7102229127"}, {"first_name"=>"André G.", "last_name"=>"Uitterlinden", "scopus_author_id"=>"35231615000"}, {"first_name"=>"Albert", "last_name"=>"Hofman", "scopus_author_id"=>"36048731400"}, {"first_name"=>"Fernando", "last_name"=>"Rivadeneira", "scopus_author_id"=>"7801419664"}, {"first_name"=>"Najaf", "last_name"=>"Amin", "scopus_author_id"=>"24329223700"}, {"first_name"=>"Lennart C.", "last_name"=>"Karssen", "scopus_author_id"=>"54796679300"}, {"first_name"=>"Johannes R.", "last_name"=>"Vingerling", "scopus_author_id"=>"6603813300"}, {"first_name"=>"Angela", "last_name"=>"Döring", "scopus_author_id"=>"7006020461"}, {"first_name"=>"Thomas", "last_name"=>"Bettecken", "scopus_author_id"=>"6603861362"}, {"first_name"=>"Goran", "last_name"=>"Bencic", "scopus_author_id"=>"57190673440"}, {"first_name"=>"Christian", "last_name"=>"Gieger", "scopus_author_id"=>"55138342700"}, {"first_name"=>"H. Erich", "last_name"=>"Wichmann", "scopus_author_id"=>"7102574024"}, {"first_name"=>"James F.", "last_name"=>"Wilson", "scopus_author_id"=>"56920724500"}, {"first_name"=>"Cristina", "last_name"=>"Venturini", "scopus_author_id"=>"55631987200"}, {"first_name"=>"Brian", "last_name"=>"Fleck", "scopus_author_id"=>"7006730276"}, {"first_name"=>"Phillippa M.", "last_name"=>"Cumberland", "scopus_author_id"=>"12902699300"}, {"first_name"=>"Jugnoo S.", "last_name"=>"Rahi", "scopus_author_id"=>"57191956020"}, {"first_name"=>"Chris J.", "last_name"=>"Hammond", "scopus_author_id"=>"7102559046"}, {"first_name"=>"Caroline", "last_name"=>"Hayward", "scopus_author_id"=>"35369845200"}, {"first_name"=>"Alan F.", "last_name"=>"Wright", "scopus_author_id"=>"35402433000"}, {"first_name"=>"Andrew D.", "last_name"=>"Paterson", "scopus_author_id"=>"55554856400"}, {"first_name"=>"Paul N.", "last_name"=>"Baird", "scopus_author_id"=>"7101685569"}, {"first_name"=>"Caroline C.W.", "last_name"=>"Klaver", "scopus_author_id"=>"6701792190"}, {"first_name"=>"Jerome I.", "last_name"=>"Rotter", "scopus_author_id"=>"56284453500"}, {"first_name"=>"Mario", "last_name"=>"Pirastu", "scopus_author_id"=>"7006656218"}, {"first_name"=>"Thomas", "last_name"=>"Meitinger", "scopus_author_id"=>"7006931003"}, {"first_name"=>"Joan E.", "last_name"=>"Bailey-Wilson", "scopus_author_id"=>"35375926200"}, {"first_name"=>"Dwight", "last_name"=>"Stambolian", "scopus_author_id"=>"7003966021"}], "year"=>2014, "source"=>"PLoS ONE", "identifiers"=>{"pui"=>"600046238", "sgr"=>"84907225028", "issn"=>"19326203", "pmid"=>"25233373", "scopus"=>"2-s2.0-84907225028", "doi"=>"10.1371/journal.pone.0107110", "isbn"=>"1081080315030"}, "id"=>"5881e453-526b-3105-baf5-56635aee4b1f", "abstract"=>"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 with hyperopia. These regions overlapped with loci on 15q14 (minimum p value = 9.11×10(-11)) and 8q12 (minimum p value 1.82×10(-11)) previously reported for MSE and myopia age at onset. We also used an intermarker linkage- disequilibrium-based method for calculating the effective number of tests in targeted regional replication analyses. We analyzed myopia (which represents the closest phenotype in our data to the one used by Kiefer et al.) and showed replication of 10 additional loci associated with myopia previously reported by Kiefer et al. This is the first replication of these loci using myopia as the trait under analysis. \"Replication-level\" association was also seen between hyperopia and 12 of Kiefer et al.'s published loci. For the loci that show evidence of association to both myopia and hyperopia, the estimated effect of the risk alleles were in opposite directions for the two traits. This suggests that these loci are important contributors to variation of refractive error across the distribution.", "link"=>"http://www.mendeley.com/research/genomewide-metaanalysis-myopia-hyperopia-provides-evidence-replication-11-loci", "reader_count"=>42, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Professor > Associate Professor"=>4, "Librarian"=>2, "Researcher"=>11, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>6, "Student > Postgraduate"=>1, "Other"=>5, "Student > Master"=>5, "Student > Bachelor"=>3, "Professor"=>2}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Professor > Associate Professor"=>4, "Librarian"=>2, "Researcher"=>11, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>6, "Student > Postgraduate"=>1, "Other"=>5, "Student > Master"=>5, "Student > Bachelor"=>3, "Professor"=>2}, "reader_count_by_subject_area"=>{"Engineering"=>2, "Unspecified"=>1, "Biochemistry, Genetics and Molecular Biology"=>5, "Mathematics"=>1, "Medicine and Dentistry"=>20, "Agricultural and Biological Sciences"=>8, "Psychology"=>1, "Social Sciences"=>1, "Computer Science"=>3}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>2}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>20}, "Social Sciences"=>{"Social Sciences"=>1}, "Psychology"=>{"Psychology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>8}, "Computer Science"=>{"Computer Science"=>3}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>5}, "Mathematics"=>{"Mathematics"=>1}, "Unspecified"=>{"Unspecified"=>1}}, "reader_count_by_country"=>{"United States"=>2, "Brazil"=>1, "Croatia"=>1}, "group_count"=>5}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1681986"], "description"=>"<p>1. SNPs which are either genome-wide significant or meet our replication threshold are highlighted in bold text. Allele frequencies for these SNPs in each of our discovery populations can be found in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0107110#pone.0107110.s018\" target=\"_blank\">Table S8</a>.</p><p>2. For each SNP reported by Kiefer <i>et al.</i>, Replication P value is the P value of that SNP in our analysis. If that SNP was not genotyped or imputed in our data, it is indicated with N/A.</p><p>3. For regions where the most significant SNP in our analysis is not the original reported SNP, that SNP is reported as Best SNP.</p><p>4. Offset is the absolute distance in base pairs to the original SNP and the P value associated with Best SNP.</p><p>5. Z scores and direction of effect for all SNPs are in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0107110#pone.0107110.s012\" target=\"_blank\">Table S2</a>.</p><p>6. This column left blank where the original SNP is the most significant SNP in the region.</p><p>7. Nearest Gene(s) indicates the closest gene by physical position for these SNPs.</p><p>Results of the replication of regions significantly associated with myopia age at onset by Kiefer <i>et al.</i><a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0107110#pone.0107110-Kiefer1\" target=\"_blank\">[18]</a> showing meta-analysis association results for each chosen SNP with myopia in our data.</p>", "links"=>[], "tags"=>["re", "association", "myopia age", "causes object images", "kora", "hyperopia", "areds", "Hyperopia Provides Evidence", "RSIII", "15 q 14", "8 q 12", "fes", "RSII", "loci", "al", "erf", "mse", "Kiefer", "11 Loci Refractive error", "mesa", "rsi"], "article_id"=>1174509, "categories"=>["Biological Sciences"], "users"=>["Claire L. Simpson", "Robert Wojciechowski", "Konrad Oexle", "Federico Murgia", "Laura Portas", "Xiaohui Li", "Virginie J. M. Verhoeven", "Veronique Vitart", "Maria Schache", "S. Mohsen Hosseini", "Pirro G. Hysi", "Leslie J. Raffel", "Mary Frances Cotch", "Emily Chew", "Barbara E. K. Klein", "Ronald Klein", "Tien Yin Wong", "Cornelia M. van Duijn", "Paul Mitchell", "Seang Mei Saw", "Maurizio Fossarello", "Jie Jin Wang", "Ozren Polašek", "Harry Campbell", "Igor Rudan", "Ben A. Oostra", "Andre G. Uitterlinden", "Albert Hofman", "Fernando Rivadeneira", "Najaf Amin", "Lennart C. Karssen", "Johannes R. Vingerling", "Angela Döring", "Thomas Bettecken", "Goran Bencic", "Christian Gieger", "H.-Erich Wichmann", "James F. Wilson", "Cristina Venturini", "Brian Fleck", "Phillippa M. Cumberland", "Jugnoo S. Rahi", "Chris J. Hammond", "Caroline Hayward", "Alan F. Wright", "Andrew D. Paterson", "Paul N. Baird", "Caroline C. W. Klaver", "Jerome I. Rotter", "Mario Pirastu", "Thomas Meitinger", "Joan E. Bailey-Wilson", "Dwight Stambolian"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0107110.t002", "stats"=>{"downloads"=>1, "page_views"=>22, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Results_of_the_replication_of_regions_significantly_associated_with_myopia_age_at_onset_by_Kiefer_et_al_18_showing_meta_analysis_association_results_for_each_chosen_SNP_with_myopia_in_our_data_/1174509", "title"=>"Results of the replication of regions significantly associated with myopia age at onset by Kiefer <i>et al.</i>[18] showing meta-analysis association results for each chosen SNP with myopia in our data.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-09-18 03:47:36"}
  • {"files"=>["https://ndownloader.figshare.com/files/1681984"], "description"=>"<p>1. For myopia, cases were defined as MSE <−1D, controls>0D and individuals between 0D and −1D coded as unknown.</p><p>2. Average MSE of all cases or controls used in the analyses.</p><p>3. For hyperopia, cases were defined as MSE>+1D, controls <0D and individuals between 0D and +1D coded as unknown.</p><p>Baseline Characteristics of the nine populations.</p>", "links"=>[], "tags"=>["re", "association", "myopia age", "causes object images", "kora", "hyperopia", "areds", "Hyperopia Provides Evidence", "RSIII", "15 q 14", "8 q 12", "fes", "RSII", "loci", "al", "erf", "mse", "Kiefer", "11 Loci Refractive error", "mesa", "rsi"], "article_id"=>1174508, "categories"=>["Biological Sciences"], "users"=>["Claire L. Simpson", "Robert Wojciechowski", "Konrad Oexle", "Federico Murgia", "Laura Portas", "Xiaohui Li", "Virginie J. M. Verhoeven", "Veronique Vitart", "Maria Schache", "S. Mohsen Hosseini", "Pirro G. Hysi", "Leslie J. Raffel", "Mary Frances Cotch", "Emily Chew", "Barbara E. K. Klein", "Ronald Klein", "Tien Yin Wong", "Cornelia M. van Duijn", "Paul Mitchell", "Seang Mei Saw", "Maurizio Fossarello", "Jie Jin Wang", "Ozren Polašek", "Harry Campbell", "Igor Rudan", "Ben A. Oostra", "Andre G. Uitterlinden", "Albert Hofman", "Fernando Rivadeneira", "Najaf Amin", "Lennart C. Karssen", "Johannes R. Vingerling", "Angela Döring", "Thomas Bettecken", "Goran Bencic", "Christian Gieger", "H.-Erich Wichmann", "James F. Wilson", "Cristina Venturini", "Brian Fleck", "Phillippa M. Cumberland", "Jugnoo S. Rahi", "Chris J. Hammond", "Caroline Hayward", "Alan F. Wright", "Andrew D. Paterson", "Paul N. Baird", "Caroline C. W. Klaver", "Jerome I. Rotter", "Mario Pirastu", "Thomas Meitinger", "Joan E. Bailey-Wilson", "Dwight Stambolian"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0107110.t001", "stats"=>{"downloads"=>5, "page_views"=>26, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Baseline_Characteristics_of_the_nine_populations_/1174508", "title"=>"Baseline Characteristics of the nine populations.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-09-18 03:47:36"}
  • {"files"=>["https://ndownloader.figshare.com/files/1681981"], "description"=>"<p>Each dot represents an observed statistic (defined as -log10 P) versus the corresponding expected statistic. The red line corresponds to the null distribution. b) Manhattan plot for association between all SNPs analyzed and myopia in the meta-analysis excluding the ERF cohort. Each dot represents an observed statistic (defined as -log10 P). The darker gray line corresponds to the genome-wide significance threshold and the lighter gray line represents the suggestive threshold.</p>", "links"=>[], "tags"=>["re", "association", "myopia age", "causes object images", "kora", "hyperopia", "areds", "Hyperopia Provides Evidence", "RSIII", "15 q 14", "8 q 12", "fes", "RSII", "loci", "al", "erf", "mse", "Kiefer", "11 Loci Refractive error", "mesa", "rsi"], "article_id"=>1174505, "categories"=>["Biological Sciences"], "users"=>["Claire L. Simpson", "Robert Wojciechowski", "Konrad Oexle", "Federico Murgia", "Laura Portas", "Xiaohui Li", "Virginie J. M. Verhoeven", "Veronique Vitart", "Maria Schache", "S. Mohsen Hosseini", "Pirro G. Hysi", "Leslie J. Raffel", "Mary Frances Cotch", "Emily Chew", "Barbara E. K. Klein", "Ronald Klein", "Tien Yin Wong", "Cornelia M. van Duijn", "Paul Mitchell", "Seang Mei Saw", "Maurizio Fossarello", "Jie Jin Wang", "Ozren Polašek", "Harry Campbell", "Igor Rudan", "Ben A. Oostra", "Andre G. Uitterlinden", "Albert Hofman", "Fernando Rivadeneira", "Najaf Amin", "Lennart C. Karssen", "Johannes R. Vingerling", "Angela Döring", "Thomas Bettecken", "Goran Bencic", "Christian Gieger", "H.-Erich Wichmann", "James F. Wilson", "Cristina Venturini", "Brian Fleck", "Phillippa M. Cumberland", "Jugnoo S. Rahi", "Chris J. Hammond", "Caroline Hayward", "Alan F. Wright", "Andrew D. Paterson", "Paul N. Baird", "Caroline C. W. Klaver", "Jerome I. Rotter", "Mario Pirastu", "Thomas Meitinger", "Joan E. Bailey-Wilson", "Dwight Stambolian"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0107110.g003", "stats"=>{"downloads"=>3, "page_views"=>24, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Q_Q_and_Manhattan_Plots_for_the_myopia_analysis_excluding_the_ERF_cohort_a_Q_8211_Q_plot_for_association_between_all_SNPs_analyzed_and_myopia_in_the_meta_analysis_excluding_the_ERF_cohort_/1174505", "title"=>"Q-Q and Manhattan Plots for the myopia analysis excluding the ERF cohort a) Q–Q plot for association between all SNPs analyzed and myopia in the meta-analysis excluding the ERF cohort.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-09-18 03:47:36"}
  • {"files"=>["https://ndownloader.figshare.com/files/1681969"], "description"=>"<p>a) Q-Q plot for association between all SNPs analyzed and hyperopia in the meta-analysis. Each dot represents an observed statistic (defined as -log10 P) versus the corresponding expected statistic. The red line corresponds to the null distribution. b) Manhattan plot for association between all SNPs analyzed and hyperopia in the meta-analysis. Each dot represents an observed statistic (defined as -log10 P). The darker gray line corresponds to the genome-wide significance threshold and the lighter gray line represents the suggestive threshold.</p>", "links"=>[], "tags"=>["re", "association", "myopia age", "causes object images", "kora", "hyperopia", "areds", "Hyperopia Provides Evidence", "RSIII", "15 q 14", "8 q 12", "fes", "RSII", "loci", "al", "erf", "mse", "Kiefer", "11 Loci Refractive error", "mesa", "rsi"], "article_id"=>1174503, "categories"=>["Biological Sciences"], "users"=>["Claire L. Simpson", "Robert Wojciechowski", "Konrad Oexle", "Federico Murgia", "Laura Portas", "Xiaohui Li", "Virginie J. M. Verhoeven", "Veronique Vitart", "Maria Schache", "S. Mohsen Hosseini", "Pirro G. Hysi", "Leslie J. Raffel", "Mary Frances Cotch", "Emily Chew", "Barbara E. K. Klein", "Ronald Klein", "Tien Yin Wong", "Cornelia M. van Duijn", "Paul Mitchell", "Seang Mei Saw", "Maurizio Fossarello", "Jie Jin Wang", "Ozren Polašek", "Harry Campbell", "Igor Rudan", "Ben A. Oostra", "Andre G. Uitterlinden", "Albert Hofman", "Fernando Rivadeneira", "Najaf Amin", "Lennart C. Karssen", "Johannes R. Vingerling", "Angela Döring", "Thomas Bettecken", "Goran Bencic", "Christian Gieger", "H.-Erich Wichmann", "James F. Wilson", "Cristina Venturini", "Brian Fleck", "Phillippa M. Cumberland", "Jugnoo S. Rahi", "Chris J. Hammond", "Caroline Hayward", "Alan F. Wright", "Andrew D. Paterson", "Paul N. Baird", "Caroline C. W. Klaver", "Jerome I. Rotter", "Mario Pirastu", "Thomas Meitinger", "Joan E. Bailey-Wilson", "Dwight Stambolian"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0107110.g002", "stats"=>{"downloads"=>3, "page_views"=>25, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Q_Q_and_Manhattan_Plots_for_the_hyperopia_analysis_of_all_cohorts_/1174503", "title"=>"Q-Q and Manhattan Plots for the hyperopia analysis of all cohorts.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-09-18 03:47:36"}
  • {"files"=>["https://ndownloader.figshare.com/files/1681987"], "description"=>"<p>1. SNPs which are either genome-wide significant or meet our replication threshold are highlighted in bold text. Allele frequencies for these SNPs in each of our discovery populations can be found in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0107110#pone.0107110.s018\" target=\"_blank\">Table S8</a>.</p><p>2. For each SNP reported by Kiefer <i>et al. </i>, Replication P value is the P value of that SNP in our analysis. If that SNP was not genotyped or imputed in our data, it is indicated with N/A.</p><p>3. For regions where the most significant SNP in our analysis is not the original reported SNP, that SNP is reported as Best SNP.</p><p>4. Offset is the absolute distance in base pairs to the original SNP and the P value associated with Best SNP.</p><p>5. Z scores and direction of effect for all SNPs are in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0107110#pone.0107110.s012\" target=\"_blank\">Table S2</a>.</p><p>6. This column left blank where the original SNP is the most significant SNP in the region.</p><p>7. Nearest Gene(s) indicates the closest gene by physical position for these SNPs.</p><p>Results of the hyperopia analyses in the regions that were significantly associated with myopia age at onset by Kiefer <i>et al.</i><a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0107110#pone.0107110-Kiefer1\" target=\"_blank\">[18]</a> showing meta-analysis association results for each chosen SNP.</p>", "links"=>[], "tags"=>["re", "association", "myopia age", "causes object images", "kora", "hyperopia", "areds", "Hyperopia Provides Evidence", "RSIII", "15 q 14", "8 q 12", "fes", "RSII", "loci", "al", "erf", "mse", "Kiefer", "11 Loci Refractive error", "mesa", "rsi"], "article_id"=>1174511, "categories"=>["Biological Sciences"], "users"=>["Claire L. Simpson", "Robert Wojciechowski", "Konrad Oexle", "Federico Murgia", "Laura Portas", "Xiaohui Li", "Virginie J. M. Verhoeven", "Veronique Vitart", "Maria Schache", "S. Mohsen Hosseini", "Pirro G. Hysi", "Leslie J. Raffel", "Mary Frances Cotch", "Emily Chew", "Barbara E. K. Klein", "Ronald Klein", "Tien Yin Wong", "Cornelia M. van Duijn", "Paul Mitchell", "Seang Mei Saw", "Maurizio Fossarello", "Jie Jin Wang", "Ozren Polašek", "Harry Campbell", "Igor Rudan", "Ben A. Oostra", "Andre G. Uitterlinden", "Albert Hofman", "Fernando Rivadeneira", "Najaf Amin", "Lennart C. Karssen", "Johannes R. Vingerling", "Angela Döring", "Thomas Bettecken", "Goran Bencic", "Christian Gieger", "H.-Erich Wichmann", "James F. Wilson", "Cristina Venturini", "Brian Fleck", "Phillippa M. Cumberland", "Jugnoo S. Rahi", "Chris J. Hammond", "Caroline Hayward", "Alan F. Wright", "Andrew D. Paterson", "Paul N. Baird", "Caroline C. W. Klaver", "Jerome I. Rotter", "Mario Pirastu", "Thomas Meitinger", "Joan E. Bailey-Wilson", "Dwight Stambolian"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0107110.t003", "stats"=>{"downloads"=>6, "page_views"=>21, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Results_of_the_hyperopia_analyses_in_the_regions_that_were_significantly_associated_with_myopia_age_at_onset_by_Kiefer_et_al_18_showing_meta_analysis_association_results_for_each_chosen_SNP_/1174511", "title"=>"Results of the hyperopia analyses in the regions that were significantly associated with myopia age at onset by Kiefer <i>et al.</i>[18] showing meta-analysis association results for each chosen SNP.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-09-18 03:47:36"}
  • {"files"=>["https://ndownloader.figshare.com/files/1681982"], "description"=>"<p>Each dot represents an observed statistic (defined as -log10 P) versus the corresponding expected statistic. The red line corresponds to the null distribution. b) Manhattan plot for association between all SNPs analyzed and hyperopia in the meta-analysis excluding the ERF cohort. Each dot represents an observed statistic (defined as -log10 P). The darker gray line corresponds to the genome-wide significance threshold and the lighter gray line represents the suggestive threshold.</p>", "links"=>[], "tags"=>["re", "association", "myopia age", "causes object images", "kora", "hyperopia", "areds", "Hyperopia Provides Evidence", "RSIII", "15 q 14", "8 q 12", "fes", "RSII", "loci", "al", "erf", "mse", "Kiefer", "11 Loci Refractive error", "mesa", "rsi"], "article_id"=>1174506, "categories"=>["Biological Sciences"], "users"=>["Claire L. Simpson", "Robert Wojciechowski", "Konrad Oexle", "Federico Murgia", "Laura Portas", "Xiaohui Li", "Virginie J. M. Verhoeven", "Veronique Vitart", "Maria Schache", "S. Mohsen Hosseini", "Pirro G. Hysi", "Leslie J. Raffel", "Mary Frances Cotch", "Emily Chew", "Barbara E. K. Klein", "Ronald Klein", "Tien Yin Wong", "Cornelia M. van Duijn", "Paul Mitchell", "Seang Mei Saw", "Maurizio Fossarello", "Jie Jin Wang", "Ozren Polašek", "Harry Campbell", "Igor Rudan", "Ben A. Oostra", "Andre G. Uitterlinden", "Albert Hofman", "Fernando Rivadeneira", "Najaf Amin", "Lennart C. Karssen", "Johannes R. Vingerling", "Angela Döring", "Thomas Bettecken", "Goran Bencic", "Christian Gieger", "H.-Erich Wichmann", "James F. Wilson", "Cristina Venturini", "Brian Fleck", "Phillippa M. Cumberland", "Jugnoo S. Rahi", "Chris J. Hammond", "Caroline Hayward", "Alan F. Wright", "Andrew D. Paterson", "Paul N. Baird", "Caroline C. W. Klaver", "Jerome I. Rotter", "Mario Pirastu", "Thomas Meitinger", "Joan E. Bailey-Wilson", "Dwight Stambolian"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0107110.g004", "stats"=>{"downloads"=>0, "page_views"=>30, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Q_Q_and_Manhattan_Plots_for_the_hyperopia_analysis_excluding_the_ERF_cohort_a_Q_Q_plot_for_association_between_all_SNPs_analyzed_and_hyperopia_in_the_meta_analysis_excluding_the_ERF_cohort_/1174506", "title"=>"Q-Q and Manhattan Plots for the hyperopia analysis excluding the ERF cohort a) Q-Q plot for association between all SNPs analyzed and hyperopia in the meta-analysis excluding the ERF cohort.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-09-18 03:47:36"}
  • {"files"=>["https://ndownloader.figshare.com/files/1681962"], "description"=>"<p>a) Q-Q plot for association between all SNPs analyzed and myopia in the meta-analysis. Each dot represents an observed statistic (defined as -log10 P) versus the corresponding expected statistic. The red line corresponds to the null distribution. b) Manhattan plot for association between all SNPs analyzed and myopia in the meta-analysis. Each dot represents an observed statistic (defined as -log10 P). The darker gray line corresponds to the genome-wide significance threshold and the lighter gray line represents the suggestive threshold.</p>", "links"=>[], "tags"=>["re", "association", "myopia age", "causes object images", "kora", "hyperopia", "areds", "Hyperopia Provides Evidence", "RSIII", "15 q 14", "8 q 12", "fes", "RSII", "loci", "al", "erf", "mse", "Kiefer", "11 Loci Refractive error", "mesa", "rsi"], "article_id"=>1174501, "categories"=>["Biological Sciences"], "users"=>["Claire L. Simpson", "Robert Wojciechowski", "Konrad Oexle", "Federico Murgia", "Laura Portas", "Xiaohui Li", "Virginie J. M. Verhoeven", "Veronique Vitart", "Maria Schache", "S. Mohsen Hosseini", "Pirro G. Hysi", "Leslie J. Raffel", "Mary Frances Cotch", "Emily Chew", "Barbara E. K. Klein", "Ronald Klein", "Tien Yin Wong", "Cornelia M. van Duijn", "Paul Mitchell", "Seang Mei Saw", "Maurizio Fossarello", "Jie Jin Wang", "Ozren Polašek", "Harry Campbell", "Igor Rudan", "Ben A. Oostra", "Andre G. Uitterlinden", "Albert Hofman", "Fernando Rivadeneira", "Najaf Amin", "Lennart C. Karssen", "Johannes R. Vingerling", "Angela Döring", "Thomas Bettecken", "Goran Bencic", "Christian Gieger", "H.-Erich Wichmann", "James F. Wilson", "Cristina Venturini", "Brian Fleck", "Phillippa M. Cumberland", "Jugnoo S. Rahi", "Chris J. Hammond", "Caroline Hayward", "Alan F. Wright", "Andrew D. Paterson", "Paul N. Baird", "Caroline C. W. Klaver", "Jerome I. Rotter", "Mario Pirastu", "Thomas Meitinger", "Joan E. Bailey-Wilson", "Dwight Stambolian"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0107110.g001", "stats"=>{"downloads"=>6, "page_views"=>25, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Q_Q_and_Manhattan_Plots_for_the_myopia_analysis_of_all_cohorts_/1174501", "title"=>"Q-Q and Manhattan Plots for the myopia analysis of all cohorts.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-09-18 03:47:36"}
  • {"files"=>["https://ndownloader.figshare.com/files/1681991", "https://ndownloader.figshare.com/files/1681992", "https://ndownloader.figshare.com/files/1681993", "https://ndownloader.figshare.com/files/1681994", "https://ndownloader.figshare.com/files/1681995", "https://ndownloader.figshare.com/files/1681996", "https://ndownloader.figshare.com/files/1681997", "https://ndownloader.figshare.com/files/1681998", "https://ndownloader.figshare.com/files/1681999", "https://ndownloader.figshare.com/files/1682000", "https://ndownloader.figshare.com/files/1682001", "https://ndownloader.figshare.com/files/1682002", "https://ndownloader.figshare.com/files/1682003", "https://ndownloader.figshare.com/files/1682004", "https://ndownloader.figshare.com/files/1682005", "https://ndownloader.figshare.com/files/1682006", "https://ndownloader.figshare.com/files/1682007", "https://ndownloader.figshare.com/files/1682008", "https://ndownloader.figshare.com/files/1682009", "https://ndownloader.figshare.com/files/1682010", "https://ndownloader.figshare.com/files/1682011", "https://ndownloader.figshare.com/files/1682012"], "description"=>"<div><p>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<sup>−8</sup>), which has been reported by Kiefer <i>et al.</i> as significantly associated with myopia age at onset and Verhoeven <i>et al.</i> as significantly associated to mean spherical-equivalent (MSE) refractive error. We observed two genome-wide significant associations with hyperopia. These regions overlapped with loci on 15q14 (minimum p value = 9.11×10<sup>−11</sup>) and 8q12 (minimum p value 1.82×10<sup>−11</sup>) previously reported for MSE and myopia age at onset. We also used an intermarker linkage- disequilibrium-based method for calculating the effective number of tests in targeted regional replication analyses. We analyzed myopia (which represents the closest phenotype in our data to the one used by Kiefer <i>et al.</i>) and showed replication of 10 additional loci associated with myopia previously reported by Kiefer <i>et al</i>. This is the first replication of these loci using myopia as the trait under analysis. “Replication-level” association was also seen between hyperopia and 12 of Kiefer <i>et al.</i>'s published loci. For the loci that show evidence of association to both myopia and hyperopia, the estimated effect of the risk alleles were in opposite directions for the two traits. This suggests that these loci are important contributors to variation of refractive error across the distribution.</p></div>", "links"=>[], "tags"=>["re", "association", "myopia age", "causes object images", "kora", "hyperopia", "areds", "Hyperopia Provides Evidence", "RSIII", "15 q 14", "8 q 12", "fes", "RSII", "loci", "al", "erf", "mse", "Kiefer", "11 Loci Refractive error", "mesa", "rsi"], "article_id"=>1174515, "categories"=>["Biological Sciences"], "users"=>["Claire L. Simpson", "Robert Wojciechowski", "Konrad Oexle", "Federico Murgia", "Laura Portas", "Xiaohui Li", "Virginie J. M. Verhoeven", "Veronique Vitart", "Maria Schache", "S. Mohsen Hosseini", "Pirro G. Hysi", "Leslie J. Raffel", "Mary Frances Cotch", "Emily Chew", "Barbara E. K. Klein", "Ronald Klein", "Tien Yin Wong", "Cornelia M. van Duijn", "Paul Mitchell", "Seang Mei Saw", "Maurizio Fossarello", "Jie Jin Wang", "Ozren Polašek", "Harry Campbell", "Igor Rudan", "Ben A. Oostra", "Andre G. Uitterlinden", "Albert Hofman", "Fernando Rivadeneira", "Najaf Amin", "Lennart C. Karssen", "Johannes R. Vingerling", "Angela Döring", "Thomas Bettecken", "Goran Bencic", "Christian Gieger", "H.-Erich Wichmann", "James F. Wilson", "Cristina Venturini", "Brian Fleck", "Phillippa M. Cumberland", "Jugnoo S. Rahi", "Chris J. Hammond", "Caroline Hayward", "Alan F. Wright", "Andrew D. Paterson", "Paul N. Baird", "Caroline C. W. Klaver", "Jerome I. Rotter", "Mario Pirastu", "Thomas Meitinger", "Joan E. 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