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{"title"=>"Runs of Homozygosity Associated with Speech Delay in Autism in a Taiwanese Han Population: Evidence for the Recessive Model", "type"=>"journal", "authors"=>[{"first_name"=>"Ping I.", "last_name"=>"Lin", "scopus_author_id"=>"24464444400"}, {"first_name"=>"Po Hsiu", "last_name"=>"Kuo", "scopus_author_id"=>"14031704600"}, {"first_name"=>"Chia Hsiang", "last_name"=>"Chen", "scopus_author_id"=>"35197794800"}, {"first_name"=>"Jer Yuarn", "last_name"=>"Wu", "scopus_author_id"=>"7409255678"}, {"first_name"=>"Susan S F", "last_name"=>"Gau", "scopus_author_id"=>"7004848762"}, {"first_name"=>"Yu Yu", "last_name"=>"Wu", "scopus_author_id"=>"54902862300"}, {"first_name"=>"Shih Kai", "last_name"=>"Liu", "scopus_author_id"=>"35279988400"}], "year"=>2013, "source"=>"PLoS ONE", "identifiers"=>{"scopus"=>"2-s2.0-84881599818", "sgr"=>"84881599818", "issn"=>"19326203", "doi"=>"10.1371/journal.pone.0072056", "pmid"=>"23977206", "pui"=>"369579407"}, "id"=>"75e8b97e-bdf0-322d-9cf4-de4382da9705", "abstract"=>"Runs of homozygosity (ROH) may play a role in complex diseases. In the current study, we aimed to test if ROHs are linked to the risk of autism and related language impairment. We analyzed 546,080 SNPs in 315 Han Chinese affected with autism and 1,115 controls. ROH was defined as an extended homozygous haplotype spanning at least 500 kb. Relative extended haplotype homozygosity (REHH) for the trait-associated ROH region was calculated to search for the signature of selection sweeps. Totally, we identified 676 ROH regions. An ROH region on 11q22.3 was significantly associated with speech delay (corrected p = 1.73×10(-8)). This region contains the NPAT and ATM genes associated with ataxia telangiectasia characterized by language impairment; the CUL5 (culin 5) gene in the same region may modulate the neuronal migration process related to language functions. These three genes are highly expressed in the cerebellum. No evidence for recent positive selection was detected on the core haplotypes in this region. The same ROH region was also nominally significantly associated with speech delay in another independent sample (p = 0.037; combinatorial analysis Stouffer's z trend = 0.0005). Taken together, our findings suggest that extended recessive loci on 11q22.3 may play a role in language impairment in autism. More research is warranted to investigate if these genes influence speech pathology by perturbing cerebellar functions.", "link"=>"http://www.mendeley.com/research/runs-homozygosity-associated-speech-delay-autism-taiwanese-han-population-evidence-recessive-model", "reader_count"=>24, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Researcher"=>3, "Student > Doctoral Student"=>4, "Student > Ph. D. Student"=>7, "Student > Master"=>2, "Other"=>3, "Student > Bachelor"=>3, "Lecturer"=>1}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Researcher"=>3, "Student > Doctoral Student"=>4, "Student > Ph. D. Student"=>7, "Student > Master"=>2, "Other"=>3, "Student > Bachelor"=>3, "Lecturer"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>1, "Biochemistry, Genetics and Molecular Biology"=>3, "Medicine and Dentistry"=>8, "Agricultural and Biological Sciences"=>4, "Neuroscience"=>2, "Psychology"=>3, "Social Sciences"=>1, "Computer Science"=>2}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>8}, "Neuroscience"=>{"Neuroscience"=>2}, "Social Sciences"=>{"Social Sciences"=>1}, "Psychology"=>{"Psychology"=>3}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>4}, "Computer Science"=>{"Computer Science"=>2}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>3}, "Unspecified"=>{"Unspecified"=>1}}, "reader_count_by_country"=>{"Taiwan"=>1}, "group_count"=>2}

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• http://doi.org/10.1007/s11682-019-00199-0
• http://doi.org/10.1186/s12864-018-4489-0
• http://doi.org/10.1007/s00438-017-1378-1
• http://doi.org/10.1007/s13311-015-0363-9
• http://doi.org/10.1007/s10802-018-0404-z
• http://doi.org/10.1038/gim.2014.118
• http://doi.org/10.1002/jbmr.2558
• http://doi.org/10.1038/nrg.2017.109
• http://doi.org/10.1016/j.ajhg.2015.06.001
• http://doi.org/10.17116/jnevro201911905191

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• {"files"=>["https://ndownloader.figshare.com/files/1173145"], "description"=>"1<p>Maternal and paternal education: 1≤6 years, 2 = 7−9 years; 3 = 10−12 years, 4 = 13−16 years, 5 = >16 years.</p>2<p>SRST: Total social responsiveness score assessed by the Autism Diagnostic Interview-revised.</p>3<p>SCQ: social communication quotient total score.</p>4<p>FSTBEH: Stereotype behavior/interest score assessed by the Autism Diagnostic Interview-revised.</p>5<p>The unit of age of phrase is month.</p>6<p>VIQ = verbal IQ; PIQ = performance IQ.</p>7<p>The unit of paternal/maternal age is year.</p>", "links"=>[], "tags"=>["Computational biology", "population genetics", "Genetic polymorphism", "Evolutionary biology", "genetics", "Population biology", "epidemiology", "Genetic epidemiology", "Mental health", "cases"], "article_id"=>775008, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Ping-I Lin", "Po-Hsiu Kuo", "Chia-Hsiang Chen", "Jer-Yuarn Wu", "Susan S-F. Gau", "Yu-Yu Wu", "Shih-Kai Liu"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0072056.t001", "stats"=>{"downloads"=>0, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Demographic_features_of_cases_in_the_discovery_population_/775008", "title"=>"Demographic features of cases in the discovery population.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-08-16 02:23:30"}
• {"files"=>["https://ndownloader.figshare.com/files/1173143"], "description"=>"<p>Panel A shows the scatter plot of REHH plotted against all core haplotype frequency (circled dot indicates the selected core haplotype “rs1074014-rs1072877-rs1564582-rs11212724-rs11211725”). Panel B shows the haplotype bifurcation diagram, which visualizes the breakdown of LD at increasing distances from core haplotypes at the selected core region. The root of each diagram is a core haplotype, identified by a dark blue circle. Panel C illustrates how the REHH value varies by the selected core haplotype. Panel D shows the table of core haplotype, and the dot in the observed haplotype sequence represents the allele that matches the ancestral. Panel E presents the theoretical phylogenetic tree of different core haplotypes. Gray squares represent haplotypes that are not present in the observed data, but are missing links in the phylogeny. The area of the squares is proportional to the frequency of the haplotype.</p>", "links"=>[], "tags"=>["Computational biology", "population genetics", "Genetic polymorphism", "Evolutionary biology", "genetics", "Population biology", "epidemiology", "Genetic epidemiology", "Mental health"], "article_id"=>775006, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Ping-I Lin", "Po-Hsiu Kuo", "Chia-Hsiang Chen", "Jer-Yuarn Wu", "Susan S-F. Gau", "Yu-Yu Wu", "Shih-Kai Liu"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0072056.g004", "stats"=>{"downloads"=>1, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_analysis_results_based_on_the_late_age_of_first_phrase_late_AFP_group_are_shown_/775006", "title"=>"The analysis results based on the late age of first phrase (late-AFP) group are shown.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-08-16 02:23:30"}
• {"files"=>["https://ndownloader.figshare.com/files/1173147"], "description"=>"*<p>Bonferroni-corrected p-value.</p>", "links"=>[], "tags"=>["Computational biology", "population genetics", "Genetic polymorphism", "Evolutionary biology", "genetics", "Population biology", "epidemiology", "Genetic epidemiology", "Mental health", "unadjusted", "p-value"], "article_id"=>775010, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Ping-I Lin", "Po-Hsiu Kuo", "Chia-Hsiang Chen", "Jer-Yuarn Wu", "Susan S-F. Gau", "Yu-Yu Wu", "Shih-Kai Liu"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0072056.t003", "stats"=>{"downloads"=>1, "page_views"=>10, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Case_only_association_test_results_for_age_of_first_phrase_only_unadjusted_p_value_8722_5_were_shown_/775010", "title"=>"Case-only association test results for age of first phrase (only unadjusted p-value <1×10⁻⁵ were shown).", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-08-16 02:23:30"}
• {"files"=>["https://ndownloader.figshare.com/files/1173142"], "description"=>"<p>Panel A shows the scatter plot of REHH plotted against all core haplotype frequency (circled dot indicates the selected core haplotype “rs1074014-rs1072877-rs1564582-rs11212724-rs11211725”). Panel B shows the haplotype bifurcation diagram, which visualizes the breakdown of LD at increasing distances from core haplotypes at the selected core region. The root of each diagram is a core haplotype, identified by a dark blue circle. Panel C illustrates how the REHH value varies by the selected core haplotype. Panel D shows the table of core haplotype, and the dot in the observed haplotype sequence represents the allele that matches the ancestral. Panel E presents the theoretical phylogenetic tree of different core haplotypes. Gray squares represent haplotypes that are not present in the observed data, but are missing links in the phylogeny. The area of the squares is proportional to the frequency of the haplotype.</p>", "links"=>[], "tags"=>["Computational biology", "population genetics", "Genetic polymorphism", "Evolutionary biology", "genetics", "Population biology", "epidemiology", "Genetic epidemiology", "Mental health", "early-afp"], "article_id"=>775005, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Ping-I Lin", "Po-Hsiu Kuo", "Chia-Hsiang Chen", "Jer-Yuarn Wu", "Susan S-F. Gau", "Yu-Yu Wu", "Shih-Kai Liu"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0072056.g003", "stats"=>{"downloads"=>3, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_analysis_results_based_on_the_early_AFP_group_are_shown_/775005", "title"=>"The analysis results based on the early-AFP group are shown.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-08-16 02:23:30"}
• {"files"=>["https://ndownloader.figshare.com/files/1173138"], "description"=>"<p>Age of first phrase (AFP) was classified into early-AFP and late-AFP groups by the k-means clustering algorithm.</p>", "links"=>[], "tags"=>["Computational biology", "population genetics", "Genetic polymorphism", "Evolutionary biology", "genetics", "Population biology", "epidemiology", "Genetic epidemiology", "Mental health", "runs", "homozygosity", "regions", "roh"], "article_id"=>775001, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Ping-I Lin", "Po-Hsiu Kuo", "Chia-Hsiang Chen", "Jer-Yuarn Wu", "Susan S-F. Gau", "Yu-Yu Wu", "Shih-Kai Liu"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0072056.g002", "stats"=>{"downloads"=>0, "page_views"=>23, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_distribution_of_runs_of_homozygosity_ROH_regions_by_length_of_the_ROH_region_is_shown_/775001", "title"=>"The distribution of runs of homozygosity (ROH) regions (by length of the ROH region) is shown.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-08-16 02:23:30"}
• {"files"=>["https://ndownloader.figshare.com/files/1173136"], "description"=>"<p>The arrow indicates the ROH region at 11q22.3.</p>", "links"=>[], "tags"=>["Computational biology", "population genetics", "Genetic polymorphism", "Evolutionary biology", "genetics", "Population biology", "epidemiology", "Genetic epidemiology", "Mental health", "findings", "presented", "p-values"], "article_id"=>774999, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Ping-I Lin", "Po-Hsiu Kuo", "Chia-Hsiang Chen", "Jer-Yuarn Wu", "Susan S-F. Gau", "Yu-Yu Wu", "Shih-Kai Liu"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0072056.g001", "stats"=>{"downloads"=>0, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_association_findings_for_age_of_first_phrase_AFP_are_presented_as_log_10_p_values_unadjusted_by_multiple_tests_across_the_whole_autosome_/774999", "title"=>"The association findings for age of first phrase (AFP) are presented as –log₁₀ p-values (unadjusted by multiple tests) across the whole autosome.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-08-16 02:23:30"}
• {"files"=>["https://ndownloader.figshare.com/files/1173150"], "description"=>"<div><p>Runs of homozygosity (ROH) may play a role in complex diseases. In the current study, we aimed to test if ROHs are linked to the risk of autism and related language impairment. We analyzed 546,080 SNPs in 315 Han Chinese affected with autism and 1,115 controls. ROH was defined as an extended homozygous haplotype spanning at least 500 kb. Relative extended haplotype homozygosity (REHH) for the trait-associated ROH region was calculated to search for the signature of selection sweeps. Totally, we identified 676 ROH regions. An ROH region on 11q22.3 was significantly associated with speech delay (corrected <i>p</i> = 1.73×10⁻⁸). This region contains the NPAT and ATM genes associated with ataxia telangiectasia characterized by language impairment; the CUL5 (culin 5) gene in the same region may modulate the neuronal migration process related to language functions. These three genes are highly expressed in the cerebellum. No evidence for recent positive selection was detected on the core haplotypes in this region. The same ROH region was also nominally significantly associated with speech delay in another independent sample (<i>p</i> = 0.037; combinatorial analysis Stouffer’s <i>z</i> trend = 0.0005). Taken together, our findings suggest that extended recessive loci on 11q22.3 may play a role in language impairment in autism. More research is warranted to investigate if these genes influence speech pathology by perturbing cerebellar functions.</p></div>", "links"=>[], "tags"=>["Computational biology", "population genetics", "Genetic polymorphism", "Evolutionary biology", "genetics", "Population biology", "epidemiology", "Genetic epidemiology", "Mental health", "homozygosity", "autism", "taiwanese", "han", "recessive"], "article_id"=>775013, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Ping-I Lin", "Po-Hsiu Kuo", "Chia-Hsiang Chen", "Jer-Yuarn Wu", "Susan S-F. Gau", "Yu-Yu Wu", "Shih-Kai Liu"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0072056", "stats"=>{"downloads"=>2, "page_views"=>14, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Runs_of_Homozygosity_Associated_with_Speech_Delay_in_Autism_in_a_Taiwanese_Han_Population_Evidence_for_the_Recessive_Model_/775013", "title"=>"Runs of Homozygosity Associated with Speech Delay in Autism in a Taiwanese Han Population: Evidence for the Recessive Model", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-08-16 02:23:30"}
• {"files"=>["https://ndownloader.figshare.com/files/1173146"], "description"=>"*<p>R_Case = prevalence rate of the ROH marker in cases; R_Ctrl = prevalence rate of the ROH marker in controls;</p>Δ<p>Unadjusted p-values based on the Fisher’s exact tests.</p>", "links"=>[], "tags"=>["Computational biology", "population genetics", "Genetic polymorphism", "Evolutionary biology", "genetics", "Population biology", "epidemiology", "Genetic epidemiology", "Mental health", "runs", "homozygosity", "regions", "nominally", "autism", "p-value"], "article_id"=>775009, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Ping-I Lin", "Po-Hsiu Kuo", "Chia-Hsiang Chen", "Jer-Yuarn Wu", "Susan S-F. Gau", "Yu-Yu Wu", "Shih-Kai Liu"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0072056.t002", "stats"=>{"downloads"=>5, "page_views"=>10, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Case_control_association_test_results_for_4_runs_of_homozygosity_ROH_regions_nominally_associated_with_the_risk_of_autism_unadjusted_p_value_lt_0_01_in_the_discovery_sample_/775009", "title"=>"Case-control association test results for 4 runs of homozygosity (ROH) regions nominally associated with the risk of autism (unadjusted p-value <0.01) in the discovery sample.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-08-16 02:23:30"}
• {"files"=>["https://ndownloader.figshare.com/files/1173144"], "description"=>"<p>Linkage disequilibrium patterns in the 11q22.3 region are shown.</p>", "links"=>[], "tags"=>["Computational biology", "population genetics", "Genetic polymorphism", "Evolutionary biology", "genetics", "Population biology", "epidemiology", "Genetic epidemiology", "Mental health", "disequilibrium", "patterns"], "article_id"=>775007, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Ping-I Lin", "Po-Hsiu Kuo", "Chia-Hsiang Chen", "Jer-Yuarn Wu", "Susan S-F. Gau", "Yu-Yu Wu", "Shih-Kai Liu"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0072056.g005", "stats"=>{"downloads"=>0, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Linkage_disequilibrium_patterns_in_the_11q22_3_region_are_shown_/775007", "title"=>"Linkage disequilibrium patterns in the 11q22.3 region are shown.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-08-16 02:23:30"}

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Relative Metric

{"start_date"=>"2013-01-01T00:00:00Z", "end_date"=>"2013-12-31T00:00:00Z", "subject_areas"=>[{"subject_area"=>"/Biology and life sciences", "average_usage"=>[269, 466, 588, 697, 800, 896, 988, 1076, 1165, 1254, 1340, 1417]}, {"subject_area"=>"/Biology and life sciences/Genetics", "average_usage"=>[284, 491, 620, 738, 843, 945, 1043, 1137, 1225, 1315, 1400, 1479, 1555]}, {"subject_area"=>"/Biology and life sciences/Neuroscience", "average_usage"=>[261, 444, 554, 655, 748, 834, 923, 1004, 1089, 1170, 1244, 1315, 1380]}, {"subject_area"=>"/People and places", "average_usage"=>[270, 456, 573, 676, 773, 867, 955, 1037, 1120, 1205, 1286, 1363, 1436]}, {"subject_area"=>"/Social sciences/Linguistics", "average_usage"=>[290, 461, 572, 671, 770, 847, 934, 1000, 1096, 1189, 1263, 1319, 1382]}, {"subject_area"=>"/Social sciences/Psychology", "average_usage"=>[294, 460, 580, 683, 777, 868, 957, 1044, 1124, 1202, 1276, 1356, 1422]}]}

F1000Prime