Digital Quantification of Human Eye Color Highlights Genetic Association of Three New Loci
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{"title"=>"Digital quantification of human eye color highlights genetic association of three new loci", "type"=>"journal", "authors"=>[{"first_name"=>"Fan", "last_name"=>"Liu", "scopus_author_id"=>"56342354400"}, {"first_name"=>"Andreas", "last_name"=>"Wollstein", "scopus_author_id"=>"14010205900"}, {"first_name"=>"Pirro G.", "last_name"=>"Hysi", "scopus_author_id"=>"18133899000"}, {"first_name"=>"Georgina A.", "last_name"=>"Ankra-Badu", "scopus_author_id"=>"12645820500"}, {"first_name"=>"Timothy D.", "last_name"=>"Spector", "scopus_author_id"=>"35351391300"}, {"first_name"=>"Daniel", "last_name"=>"Park", "scopus_author_id"=>"57191497299"}, {"first_name"=>"Gu", "last_name"=>"Zhu", "scopus_author_id"=>"7402633012"}, {"first_name"=>"Mats", "last_name"=>"Larsson", "scopus_author_id"=>"36239892200"}, {"first_name"=>"David L.", "last_name"=>"Duffy", "scopus_author_id"=>"7101657174"}, {"first_name"=>"Grant W.", "last_name"=>"Montgomery", "scopus_author_id"=>"8739667300"}, {"first_name"=>"David A.", "last_name"=>"Mackey", "scopus_author_id"=>"36909266400"}, {"first_name"=>"Susan", "last_name"=>"Walsh", "scopus_author_id"=>"56235650700"}, {"first_name"=>"Oscar", "last_name"=>"Lao", "scopus_author_id"=>"56001576300"}, {"first_name"=>"Albert", "last_name"=>"Hofman", "scopus_author_id"=>"36048731400"}, {"first_name"=>"Fernando", "last_name"=>"Rivadeneira", "scopus_author_id"=>"7801419664"}, {"first_name"=>"Johannes R.", "last_name"=>"Vingerling", "scopus_author_id"=>"6603813300"}, {"first_name"=>"Andr?? G.", "last_name"=>"Uitterlinden", "scopus_author_id"=>"35231615000"}, {"first_name"=>"Nicholas G.", "last_name"=>"Martin", "scopus_author_id"=>"35376988300"}, {"first_name"=>"Christopher J.", "last_name"=>"Hammond", "scopus_author_id"=>"7102559046"}, {"first_name"=>"Manfred", "last_name"=>"Kayser", "scopus_author_id"=>"26643477000"}], "year"=>2010, "source"=>"PLoS Genetics", "identifiers"=>{"isbn"=>"2200820186", "pmid"=>"20463881", "pui"=>"358963186", "scopus"=>"2-s2.0-77953194221", "doi"=>"10.1371/journal.pgen.1000934", "issn"=>"15537390", "sgr"=>"77953194221"}, "id"=>"699b79d2-f66d-336b-9063-6117abae626d", "abstract"=>"Previous studies have successfully identified genetic variants in several genes associated with human iris (eye) color; however, they all used simplified categorical trait information. Here, we quantified continuous eye color variation into hue and saturation values using high-resolution digital full-eye photographs and conducted a genome-wide association study on 5,951 Dutch Europeans from the Rotterdam Study. Three new regions, 1q42.3, 17q25.3, and 21q22.13, were highlighted meeting the criterion for genome-wide statistically significant association. The latter two loci were replicated in 2,261 individuals from the UK and in 1,282 from Australia. The LYST gene at 1q42.3 and the DSCR9 gene at 21q22.13 serve as promising functional candidates. A model for predicting quantitative eye colors explained over 50% of trait variance in the Rotterdam Study. Over all our data exemplify that fine phenotyping is a useful strategy for finding genes involved in human complex traits.", "link"=>"http://www.mendeley.com/research/digital-quantification-human-eye-color-highlights-genetic-association-three-new-loci-3", "reader_count"=>90, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>7, "Researcher"=>24, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>25, "Student > Postgraduate"=>6, "Student > Master"=>11, "Other"=>2, "Student > Bachelor"=>6, "Lecturer > Senior Lecturer"=>2, "Professor"=>5}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>7, "Researcher"=>24, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>25, "Student > Postgraduate"=>6, "Student > Master"=>11, "Other"=>2, "Student > Bachelor"=>6, "Lecturer > Senior Lecturer"=>2, "Professor"=>5}, "reader_count_by_subject_area"=>{"Biochemistry, Genetics and Molecular Biology"=>7, "Agricultural and Biological Sciences"=>67, "Medicine and Dentistry"=>8, "Arts and Humanities"=>1, "Veterinary Science and Veterinary Medicine"=>1, "Psychology"=>1, "Social Sciences"=>2, "Computer Science"=>2, "Immunology and Microbiology"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>8}, "Social Sciences"=>{"Social Sciences"=>2}, "Psychology"=>{"Psychology"=>1}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>67}, "Computer Science"=>{"Computer Science"=>2}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>7}, "Arts and Humanities"=>{"Arts and Humanities"=>1}, "Veterinary Science and Veterinary Medicine"=>{"Veterinary Science and Veterinary Medicine"=>1}}, "reader_count_by_country"=>{"Canada"=>1, "Austria"=>1, "Argentina"=>1, "Iran"=>1, "Hungary"=>1, "United States"=>7, "Brazil"=>1, "Thailand"=>1, "Germany"=>2}, "group_count"=>4}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/851344"], "description"=>"<p>NS: not significant.</p><p>Beta, se, and P values were derived in RS1 and RS2 cohorts, R<sup>2</sup> changes were estimated in RS3 cohort.</p><p>The interaction terms are defined at the multiplicative scale.</p><p>*rs12913832 A allele is modeled to have a dominant effect, allelic effects in other SNPs are modeled additively.</p><p>The main effect of rs16891982C is not significant when the interaction term is included.</p>", "links"=>[], "tags"=>["quantitative", "rotterdam"], "article_id"=>521760, "categories"=>["Medicine", "Neuroscience", "Genetics"], "users"=>["Fan Liu", "Andreas Wollstein", "Pirro G. Hysi", "Georgina A. Ankra-Badu", "Timothy D. Spector", "Daniel Park", "Gu Zhu", "Mats Larsson", "David L. Duffy", "Grant W. Montgomery", "David A. Mackey", "Susan Walsh", "Oscar Lao", "Albert Hofman", "Fernando Rivadeneira", "Johannes R. Vingerling", "Andre G. Uitterlinden", "Nicholas G. Martin", "Christopher J. Hammond", "Manfred Kayser"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1000934.t003", "stats"=>{"downloads"=>1, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Predicting_quantitative_eye_color_in_Rotterdam_Studies_/521760", "title"=>"Predicting quantitative eye color in Rotterdam Studies.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2010-05-06 00:29:20"}
  • {"files"=>["https://ndownloader.figshare.com/files/850671"], "description"=>"<p>The −log10 P values for association with 6 eye color traits (hue, saturation, C<sub>HS1</sub>, C<sub>HS2</sub>, 3-category classification, 5-category classification) are plotted for each genotyped SNP according to its chromosomal position (NCBI build 36). The distance between each tick on the x-axis represents 50 Mb. The P values smaller than 10<sup>−12</sup> are truncated at the level of 12 at the log scale and those greater than 0.01 are not shown. (A) P values are adjusted for age, sex and population stratification, (B) additionally adjusted for the effect of rs12913832 in <i>HERC2</i>, the most significantly associated eye color SNP known before, and (C) additionally adjusted for the effect of all 7 previously known eye color associated genes. Previously known eye color genes with genome-wide significant eye color association in the present study are noted using blue text above the figure and genes in the three newly identified loci in the 3rd scan are noted in red.</p>", "links"=>[], "tags"=>["manhattan", "quantitative", "categorical", "rotterdam"], "article_id"=>521089, "categories"=>["Medicine", "Neuroscience", "Genetics"], "users"=>["Fan Liu", "Andreas Wollstein", "Pirro G. Hysi", "Georgina A. Ankra-Badu", "Timothy D. Spector", "Daniel Park", "Gu Zhu", "Mats Larsson", "David L. Duffy", "Grant W. Montgomery", "David A. Mackey", "Susan Walsh", "Oscar Lao", "Albert Hofman", "Fernando Rivadeneira", "Johannes R. Vingerling", "Andre G. Uitterlinden", "Nicholas G. Martin", "Christopher J. Hammond", "Manfred Kayser"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1000934.g003", "stats"=>{"downloads"=>1, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_GWA_Manhattan_plot_for_quantitative_and_categorical_eye_color_in_the_Rotterdam_Study_RS123_/521089", "title"=>"GWA Manhattan plot for quantitative and categorical eye color in the Rotterdam Study (RS123).", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2010-05-06 00:18:09"}
  • {"files"=>["https://ndownloader.figshare.com/files/850260"], "description"=>"<p>(A) The Hue-Saturation (H-S) eye color space; (B) Example eye photos at their respective position in the H-S space; (C) 3 color categories defined by an ophthalmologist during eye examination and highlighted in the H-S space; (D) 5 categories defined by two researchers from digital full eye size photographs used for digital quantitative extraction of eye colors; (E) 4 quartiles of the 1st principle component C<sub>HS1</sub>; and (F) 4 quartiles of the 2nd principle component C<sub>HS2</sub>; all depicted on the H-S color space.</p>", "links"=>[], "tags"=>["hue-saturation", "rotterdam"], "article_id"=>520677, "categories"=>["Medicine", "Neuroscience", "Genetics"], "users"=>["Fan Liu", "Andreas Wollstein", "Pirro G. Hysi", "Georgina A. Ankra-Badu", "Timothy D. Spector", "Daniel Park", "Gu Zhu", "Mats Larsson", "David L. Duffy", "Grant W. Montgomery", "David A. Mackey", "Susan Walsh", "Oscar Lao", "Albert Hofman", "Fernando Rivadeneira", "Johannes R. Vingerling", "Andre G. Uitterlinden", "Nicholas G. Martin", "Christopher J. Hammond", "Manfred Kayser"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1000934.g001", "stats"=>{"downloads"=>1, "page_views"=>10, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_Hue_Saturation_H_S_eye_color_space_in_the_Rotterdam_Study_RS123_/520677", "title"=>"The Hue-Saturation (H-S) eye color space in the Rotterdam Study (RS123).", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2010-05-06 00:11:17"}
  • {"files"=>["https://ndownloader.figshare.com/files/850972"], "description"=>"<p>The chromosome 17 77.05–77.35 Mb region includes multiple small genes, SNPs rs7219915, rs9894429, and rs12452184 showed genome-wide significant association with multiple traits.</p>", "links"=>[], "tags"=>["quantitative", "rotterdam"], "article_id"=>521383, "categories"=>["Medicine", "Neuroscience", "Genetics"], "users"=>["Fan Liu", "Andreas Wollstein", "Pirro G. Hysi", "Georgina A. Ankra-Badu", "Timothy D. Spector", "Daniel Park", "Gu Zhu", "Mats Larsson", "David L. Duffy", "Grant W. Montgomery", "David A. Mackey", "Susan Walsh", "Oscar Lao", "Albert Hofman", "Fernando Rivadeneira", "Johannes R. Vingerling", "Andre G. Uitterlinden", "Nicholas G. Martin", "Christopher J. Hammond", "Manfred Kayser"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1000934.g005", "stats"=>{"downloads"=>2, "page_views"=>15, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Chromosome_17q25_3_associated_with_quantitative_eye_color_in_the_Rotterdam_Study_RS123_/521383", "title"=>"Chromosome 17q25.3 associated with quantitative eye color in the Rotterdam Study (RS123).", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2010-05-06 00:23:03"}
  • {"files"=>["https://ndownloader.figshare.com/files/851432"], "description"=>"<p>EA, the effect allele based on which beta was derived.</p><p>RS123, merged data of Rotterdam Study 1, 2, and 3.</p><p>In TwinsUK SNPs at 17q25.3 were associated with S and C<sub>HS2</sub> (P<0.02).</p>", "links"=>[], "tags"=>["snps", "rotterdam", "replication", "analyses", "twinsuk", "brisbane", "nevus"], "article_id"=>521835, "categories"=>["Medicine", "Neuroscience", "Genetics"], "users"=>["Fan Liu", "Andreas Wollstein", "Pirro G. Hysi", "Georgina A. Ankra-Badu", "Timothy D. Spector", "Daniel Park", "Gu Zhu", "Mats Larsson", "David L. Duffy", "Grant W. Montgomery", "David A. Mackey", "Susan Walsh", "Oscar Lao", "Albert Hofman", "Fernando Rivadeneira", "Johannes R. Vingerling", "Andre G. Uitterlinden", "Nicholas G. Martin", "Christopher J. Hammond", "Manfred Kayser"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1000934.t002", "stats"=>{"downloads"=>6, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_New_SNPs_associated_with_eye_color_in_Rotterdam_Studies_and_replication_analyses_in_TwinsUK_Study_and_Brisbane_Twin_Nevus_Study_BTNS_/521835", "title"=>"New SNPs associated with eye color in Rotterdam Studies, and replication analyses in TwinsUK Study and Brisbane Twin Nevus Study (BTNS).", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2010-05-06 00:30:35"}
  • {"files"=>["https://ndownloader.figshare.com/files/851256"], "description"=>"<p>Raw values, percentages, or means and standard deviations.</p><p>High resolution digital full eye size photos were available in Rotterdam Studies (RS1-3) and Brisbane Twin Nevus Study (BTNS), whereas in the Twin Study from the UK (TwinsUK) only digital full size portrait photos were available with low iris resolution.</p>", "links"=>[], "tags"=>["details", "demographics"], "article_id"=>521676, "categories"=>["Medicine", "Neuroscience", "Genetics"], "users"=>["Fan Liu", "Andreas Wollstein", "Pirro G. Hysi", "Georgina A. Ankra-Badu", "Timothy D. Spector", "Daniel Park", "Gu Zhu", "Mats Larsson", "David L. Duffy", "Grant W. Montgomery", "David A. Mackey", "Susan Walsh", "Oscar Lao", "Albert Hofman", "Fernando Rivadeneira", "Johannes R. Vingerling", "Andre G. Uitterlinden", "Nicholas G. Martin", "Christopher J. Hammond", "Manfred Kayser"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1000934.t001", "stats"=>{"downloads"=>1, "page_views"=>11, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Eye_color_details_and_demographics_of_the_study_subjects_/521676", "title"=>"Eye color details and demographics of the study subjects.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2010-05-06 00:27:56"}
  • {"files"=>["https://ndownloader.figshare.com/files/423169", "https://ndownloader.figshare.com/files/423213", "https://ndownloader.figshare.com/files/423250", "https://ndownloader.figshare.com/files/423285", "https://ndownloader.figshare.com/files/423321", "https://ndownloader.figshare.com/files/423376"], "description"=>"<div><p>Previous studies have successfully identified genetic variants in several genes associated with human iris (eye) color; however, they all used simplified categorical trait information. Here, we quantified continuous eye color variation into hue and saturation values using high-resolution digital full-eye photographs and conducted a genome-wide association study on 5,951 Dutch Europeans from the Rotterdam Study. Three new regions, 1q42.3, 17q25.3, and 21q22.13, were highlighted meeting the criterion for genome-wide statistically significant association. The latter two loci were replicated in 2,261 individuals from the UK and in 1,282 from Australia. The <em>LYST</em> gene at 1q42.3 and the <em>DSCR9</em> gene at 21q22.13 serve as promising functional candidates. A model for predicting quantitative eye colors explained over 50% of trait variance in the Rotterdam Study. Over all our data exemplify that fine phenotyping is a useful strategy for finding genes involved in human complex traits.</p></div>", "links"=>[], "tags"=>["quantification", "highlights", "loci"], "article_id"=>143568, "categories"=>["Medicine", "Neuroscience", "Genetics"], "users"=>["Fan Liu", "Andreas Wollstein", "Pirro G. Hysi", "Georgina A. Ankra-Badu", "Timothy D. Spector", "Daniel Park", "Gu Zhu", "Mats Larsson", "David L. Duffy", "Grant W. Montgomery", "David A. Mackey", "Susan Walsh", "Oscar Lao", "Albert Hofman", "Fernando Rivadeneira", "Johannes R. Vingerling", "Andre G. Uitterlinden", "Nicholas G. Martin", "Christopher J. Hammond", "Manfred Kayser"], "doi"=>["https://dx.doi.org/10.1371/journal.pgen.1000934.s001", "https://dx.doi.org/10.1371/journal.pgen.1000934.s002", "https://dx.doi.org/10.1371/journal.pgen.1000934.s003", "https://dx.doi.org/10.1371/journal.pgen.1000934.s004", "https://dx.doi.org/10.1371/journal.pgen.1000934.s005", "https://dx.doi.org/10.1371/journal.pgen.1000934.s006"], "stats"=>{"downloads"=>55, "page_views"=>11, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Digital_Quantification_of_Human_Eye_Color_Highlights_Genetic_Association_of_Three_New_Loci/143568", "title"=>"Digital Quantification of Human Eye Color Highlights Genetic Association of Three New Loci", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2010-05-06 00:59:28"}
  • {"files"=>["https://ndownloader.figshare.com/files/850830"], "description"=>"<p>Regional association plots for 300 Kb surrounding the three newly identified eye color locus on chromosomal 1q42.3. Statistical significance of associated SNPs at each locus are shown on the −log(P) scale as a function of chromosomal position. P values were derived for 6 eye color traits (see figure legend). Genes in the region and LD patterns according to HapMap version 21a CEU samples are aligned bellow. Chromosome 1 233.85–234.25 Mb region includes the <i>LYST</i> gene, where SNPs rs3768056 and rs9782955 showed genome-wide significant association with saturation only.</p>", "links"=>[], "tags"=>["quantitative", "rotterdam"], "article_id"=>521242, "categories"=>["Medicine", "Neuroscience", "Genetics"], "users"=>["Fan Liu", "Andreas Wollstein", "Pirro G. Hysi", "Georgina A. Ankra-Badu", "Timothy D. Spector", "Daniel Park", "Gu Zhu", "Mats Larsson", "David L. Duffy", "Grant W. Montgomery", "David A. Mackey", "Susan Walsh", "Oscar Lao", "Albert Hofman", "Fernando Rivadeneira", "Johannes R. Vingerling", "Andre G. Uitterlinden", "Nicholas G. Martin", "Christopher J. Hammond", "Manfred Kayser"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1000934.g004", "stats"=>{"downloads"=>2, "page_views"=>21, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Chromosome_1q42_3_associated_with_quantitative_eye_color_in_the_Rotterdam_Study_RS123_/521242", "title"=>"Chromosome 1q42.3 associated with quantitative eye color in the Rotterdam Study (RS123).", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2010-05-06 00:20:42"}
  • {"files"=>["https://ndownloader.figshare.com/files/851111"], "description"=>"<p>The chromosome 21 37.30–37.65 Mb region includes <i>DSCR6</i>, <i>PIGP</i>, <i>TTC3</i>, <i>DSCR9</i>, and <i>DSCR3</i> genes, SNPs rs1003719, rs2252893, rs2835621, rs2835630, and rs7277820 showed genome-wide significant association with C<sub>HS1</sub>.</p>", "links"=>[], "tags"=>["locus", "quantitative", "rotterdam"], "article_id"=>521534, "categories"=>["Medicine", "Neuroscience", "Genetics"], "users"=>["Fan Liu", "Andreas Wollstein", "Pirro G. Hysi", "Georgina A. Ankra-Badu", "Timothy D. Spector", "Daniel Park", "Gu Zhu", "Mats Larsson", "David L. Duffy", "Grant W. Montgomery", "David A. Mackey", "Susan Walsh", "Oscar Lao", "Albert Hofman", "Fernando Rivadeneira", "Johannes R. Vingerling", "Andre G. Uitterlinden", "Nicholas G. Martin", "Christopher J. Hammond", "Manfred Kayser"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1000934.g006", "stats"=>{"downloads"=>1, "page_views"=>15, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Chromosome_21q22_13_locus_associated_with_quantitative_eye_color_in_the_Rotterdam_Study_RS123_/521534", "title"=>"Chromosome 21q22.13 locus associated with quantitative eye color in the Rotterdam Study (RS123).", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2010-05-06 00:25:34"}
  • {"files"=>["https://ndownloader.figshare.com/files/850478"], "description"=>"<p>Observed −log<sub>10</sub> P values in a GWA of C<sub>HS1</sub> are ranked on the y-axis and plotted against the expected distribution under the null on the x-axis. All P values smaller than 10<sup>−10</sup> were truncated at 10 at the log scale. The red dots are the P values excluding the effects of sex, age, and population stratification. Blue dots are the P values excluding the effects of 7 genes previously known to be involved in eye color. Green dots are the P values after additionally excluding the effects of 3 newly identified loci, with no more SNPs showing significant association at the genome-wide level.</p>", "links"=>[], "tags"=>["rotterdam"], "article_id"=>520895, "categories"=>["Medicine", "Neuroscience", "Genetics"], "users"=>["Fan Liu", "Andreas Wollstein", "Pirro G. Hysi", "Georgina A. Ankra-Badu", "Timothy D. Spector", "Daniel Park", "Gu Zhu", "Mats Larsson", "David L. Duffy", "Grant W. Montgomery", "David A. Mackey", "Susan Walsh", "Oscar Lao", "Albert Hofman", "Fernando Rivadeneira", "Johannes R. Vingerling", "Andre G. Uitterlinden", "Nicholas G. Martin", "Christopher J. Hammond", "Manfred Kayser"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1000934.g002", "stats"=>{"downloads"=>1, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Observed_and_expected_P_values_for_eye_color_in_the_Rotterdam_Study_RS123_/520895", "title"=>"Observed and expected P values for eye color in the Rotterdam Study (RS123).", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2010-05-06 00:14:55"}

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