A Multi-Breed Genome-Wide Association Analysis for Canine Hypothyroidism Identifies a Shared Major Risk Locus on CFA12
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{"title"=>"A multi-breed genome-wide association analysis for canine Hypothyroidism identifies a shared major risk locus on CFA12", "type"=>"journal", "authors"=>[{"first_name"=>"Matteo", "last_name"=>"Bianchi", "scopus_author_id"=>"56883784000"}, {"first_name"=>"Stina", "last_name"=>"Dahlgren", "scopus_author_id"=>"56884142800"}, {"first_name"=>"Jonathan", "last_name"=>"Massey", "scopus_author_id"=>"55533307400"}, {"first_name"=>"Elisabeth", "last_name"=>"Dietschi", "scopus_author_id"=>"6603215921"}, {"first_name"=>"Marcin", "last_name"=>"Kierczak", "scopus_author_id"=>"15124018000"}, {"first_name"=>"Martine", "last_name"=>"Lund-Ziener", "scopus_author_id"=>"56884636000"}, {"first_name"=>"Katarina", "last_name"=>"Sundberg", "scopus_author_id"=>"36544481200"}, {"first_name"=>"Stein Istre", "last_name"=>"Thoresen", "scopus_author_id"=>"7005628242"}, {"first_name"=>"Olle", "last_name"=>"Kämpe", "scopus_author_id"=>"7004040462"}, {"first_name"=>"Göran", "last_name"=>"Andersson", "scopus_author_id"=>"55712441600"}, {"first_name"=>"William E.R.", "last_name"=>"Ollier", "scopus_author_id"=>"7103047807"}, {"first_name"=>"Åke", "last_name"=>"Hedhammar", "scopus_author_id"=>"7004196747"}, {"first_name"=>"Tosso", "last_name"=>"Leeb", "scopus_author_id"=>"7006758115"}, {"first_name"=>"Kerstin", "last_name"=>"Lindblad-Toh", "scopus_author_id"=>"6603065092"}, {"first_name"=>"Lorna J.", "last_name"=>"Kennedy", "scopus_author_id"=>"7202974656"}, {"first_name"=>"Frode", "last_name"=>"Lingaas", "scopus_author_id"=>"6701402743"}, {"first_name"=>"Gerli Rosengren", "last_name"=>"Pielberg", "scopus_author_id"=>"9234689700"}], "year"=>2015, "source"=>"PLoS ONE", "identifiers"=>{"issn"=>"19326203", "scopus"=>"2-s2.0-84942910144", "pmid"=>"26261983", "doi"=>"10.1371/journal.pone.0134720", "pui"=>"606195831", "isbn"=>"0300-8630 (Print)\r0300-8630 (Linking)", "sgr"=>"84942910144"}, "id"=>"21329552-0a40-3011-8d1d-c0a61fb2247f", "abstract"=>"Hypothyroidism is a complex clinical condition found in both humans and dogs, thought to be caused by a combination of genetic and environmental factors. In this study we present a multi-breed analysis of predisposing genetic risk factors for hypothyroidism in dogs using three high-risk breeds—the Gordon Setter, Hovawart and the Rhodesian Ridgeback. Using a genome-wide association approach and meta-analysis, we identified a major hypothyroidism risk locus shared by these breeds on chromosome 12 (p = 2.1x10 -11). Further characterisa-tion of the candidate region revealed a shared ~167 kb risk haplotype (4,915,018–5,081,823 bp), tagged by two SNPs in almost complete linkage disequilibrium. This breed-shared risk haplotype includes three genes (LHFPL5, SRPK1 and SLC26A8) and does not extend to the dog leukocyte antigen (DLA) class II gene cluster located in the vicinity. These three genes have not been identified as candidate genes for hypothyroid disease previously, but have functions that could potentially contribute to the development of the disease. Our results impli-cate the potential involvement of novel genes and pathways for the development of canine hypothyroidism, raising new possibilities for screening, breeding programmes and treatments in dogs. This study may also contribute to our understanding of the genetic etiology of human hypothyroid disease, which is one of the most common endocrine disorders in humans.", "link"=>"http://www.mendeley.com/research/multibreed-genomewide-association-analysis-canine-hypothyroidism-identifies-shared-major-risk-locus", "reader_count"=>20, "reader_count_by_academic_status"=>{"Unspecified"=>2, "Professor > Associate Professor"=>1, "Researcher"=>4, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>5, "Student > Postgraduate"=>1, "Student > Master"=>1, "Student > Bachelor"=>2, "Professor"=>2}, "reader_count_by_user_role"=>{"Unspecified"=>2, "Professor > Associate Professor"=>1, "Researcher"=>4, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>5, "Student > Postgraduate"=>1, "Student > Master"=>1, "Student > Bachelor"=>2, "Professor"=>2}, "reader_count_by_subject_area"=>{"Unspecified"=>4, "Mathematics"=>1, "Agricultural and Biological Sciences"=>6, "Medicine and Dentistry"=>2, "Neuroscience"=>1, "Veterinary Science and Veterinary Medicine"=>6}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>2}, "Neuroscience"=>{"Neuroscience"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>6}, "Mathematics"=>{"Mathematics"=>1}, "Unspecified"=>{"Unspecified"=>4}, "Veterinary Science and Veterinary Medicine"=>{"Veterinary Science and Veterinary Medicine"=>6}}, "reader_count_by_country"=>{"United States"=>1}, "group_count"=>2}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/2208798"], "description"=>"<p>The red lines show theoretical distribution in absence of association and theoretical confidence intervals.</p>", "links"=>[], "tags"=>["human", "26A", "candidate", "factor", "hypothyroid disease", "hypothyroidism risk locus", "CFA 12 Hypothyroidism", "Canine Hypothyroidism Identifies", "snp", "SRPK", "LHFPL", "dla", "haplotype", "Shared Major Risk Locus", "breed", "class II gene cluster", "dog leukocyte antigen", "slc"], "article_id"=>1508224, "categories"=>["Biological Sciences"], "users"=>["Matteo Bianchi", "Stina Dahlgren", "Jonathan Massey", "Elisabeth Dietschi", "Marcin Kierczak", "Martine Lund-Ziener", "Katarina Sundberg", "Stein Istre Thoresen", "Olle Kämpe", "Göran Andersson", "William E. R. Ollier", "Åke Hedhammar", "Tosso Leeb", "Kerstin Lindblad-Toh", "Lorna J. Kennedy", "Frode Lingaas", "Gerli Rosengren Pielberg"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0134720.g004", "stats"=>{"downloads"=>3, "page_views"=>54, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Meta_analysis_a_MDS_plot_showing_genetic_distances_between_GS_HV_and_RR_sample_sets_and_b_QQ_plot_showing_no_inflation_955_0_977_/1508224", "title"=>"Meta-analysis (a) MDS plot showing genetic distances between GS, HV and RR sample sets and (b) QQ plot showing no inflation (λ = 0.977).", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-08-11 03:40:54"}
  • {"files"=>["https://ndownloader.figshare.com/files/2208796"], "description"=>"<p>Orange bars are highlighting the associated regions (R<sup>2</sup> ≥ 0.7) in GS (3,022,017–9,637,877 bp), HV (4,110,982–6,635,695 bp) and RR (3,561,421–9,336,752 bp). Dashed lines indicate the shared region of association (4,110,982–6,635,695 bp).</p>", "links"=>[], "tags"=>["human", "26A", "candidate", "factor", "hypothyroid disease", "hypothyroidism risk locus", "CFA 12 Hypothyroidism", "Canine Hypothyroidism Identifies", "snp", "SRPK", "LHFPL", "dla", "haplotype", "Shared Major Risk Locus", "breed", "class II gene cluster", "dog leukocyte antigen", "slc"], "article_id"=>1508222, "categories"=>["Biological Sciences"], "users"=>["Matteo Bianchi", "Stina Dahlgren", "Jonathan Massey", "Elisabeth Dietschi", "Marcin Kierczak", "Martine Lund-Ziener", "Katarina Sundberg", "Stein Istre Thoresen", "Olle Kämpe", "Göran Andersson", "William E. R. Ollier", "Åke Hedhammar", "Tosso Leeb", "Kerstin Lindblad-Toh", "Lorna J. Kennedy", "Frode Lingaas", "Gerli Rosengren Pielberg"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0134720.g003", "stats"=>{"downloads"=>3, "page_views"=>90, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Breed_specific_LD_Manhattan_plots_of_relevant_region_on_CFA12_indicating_R_2_values_of_each_SNP_in_respect_to_the_highest_associated_markers_/1508222", "title"=>"Breed-specific LD Manhattan plots of relevant region on CFA12, indicating R<sup>2</sup>-values of each SNP in respect to the highest associated markers.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-08-11 03:40:54"}
  • {"files"=>["https://ndownloader.figshare.com/files/2208792"], "description"=>"<p>(a-c) MDS plots showing homogenous sample sets without presence of clustered samples in the (a) Gordon Setter (GS), (b) Hovawart (HV) and (c) Rhodesian Ridgeback (RR) breed cohorts. (d-f) QQ plots showing no inflation after the mixed model approach, and the empirical genome-wide significance thresholds (indicated by red lines and their corresponding values) and empirical 95% confidence intervals (CI<sub>95</sub>) in (d) GS λ = 1.019, (e) HV λ = 0.995 and (f) RR λ = 0.996.</p>", "links"=>[], "tags"=>["human", "26A", "candidate", "factor", "hypothyroid disease", "hypothyroidism risk locus", "CFA 12 Hypothyroidism", "Canine Hypothyroidism Identifies", "snp", "SRPK", "LHFPL", "dla", "haplotype", "Shared Major Risk Locus", "breed", "class II gene cluster", "dog leukocyte antigen", "slc"], "article_id"=>1508218, "categories"=>["Biological Sciences"], "users"=>["Matteo Bianchi", "Stina Dahlgren", "Jonathan Massey", "Elisabeth Dietschi", "Marcin Kierczak", "Martine Lund-Ziener", "Katarina Sundberg", "Stein Istre Thoresen", "Olle Kämpe", "Göran Andersson", "William E. R. Ollier", "Åke Hedhammar", "Tosso Leeb", "Kerstin Lindblad-Toh", "Lorna J. Kennedy", "Frode Lingaas", "Gerli Rosengren Pielberg"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0134720.g001", "stats"=>{"downloads"=>0, "page_views"=>19, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_A_Multi_Breed_Genome_Wide_Association_Analysis_for_Canine_Hypothyroidism_Identifies_a_Shared_Major_Risk_Locus_on_CFA12_Fig_1_/1508218", "title"=>"A Multi-Breed Genome-Wide Association Analysis for Canine Hypothyroidism Identifies a Shared Major Risk Locus on CFA12 - Fig 1", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-08-11 03:40:54"}
  • {"files"=>["https://ndownloader.figshare.com/files/2208800"], "description"=>"<p>P<sub>raw</sub>—uncorrected p-value for the strongest association, OR—Odds ratio, CI<sub>OR</sub>—OR 95% Confidence Intervals, P<sub>genome</sub>—empirical genome-wide significance levels obtained after 1000 permutations, CI<sub>95</sub>—95% empirical SNP distributions confidence intervals, NA—not applicable.</p><p>Summary of the three single-breed GWA analysis results.</p>", "links"=>[], "tags"=>["human", "26A", "candidate", "factor", "hypothyroid disease", "hypothyroidism risk locus", "CFA 12 Hypothyroidism", "Canine Hypothyroidism Identifies", "snp", "SRPK", "LHFPL", "dla", "haplotype", "Shared Major Risk Locus", "breed", "class II gene cluster", "dog leukocyte antigen", "slc"], "article_id"=>1508226, "categories"=>["Biological Sciences"], "users"=>["Matteo Bianchi", "Stina Dahlgren", "Jonathan Massey", "Elisabeth Dietschi", "Marcin Kierczak", "Martine Lund-Ziener", "Katarina Sundberg", "Stein Istre Thoresen", "Olle Kämpe", "Göran Andersson", "William E. R. Ollier", "Åke Hedhammar", "Tosso Leeb", "Kerstin Lindblad-Toh", "Lorna J. Kennedy", "Frode Lingaas", "Gerli Rosengren Pielberg"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0134720.t001", "stats"=>{"downloads"=>3, "page_views"=>24, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Summary_of_the_three_single_breed_GWA_analysis_results_/1508226", "title"=>"Summary of the three single-breed GWA analysis results.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2015-08-11 03:40:54"}
  • {"files"=>["https://ndownloader.figshare.com/files/2208794"], "description"=>"<p>Manhattan plots showing a common peak on CFA12 in (a) GS p<sub>raw</sub> = 2.4x10<sup>-8</sup>, (b) HV p<sub>raw</sub> = 4.2x10<sup>-6</sup>, (c) RR p<sub>raw</sub> = 2.0x10<sup>-5</sup> and (d) multi-breed meta-analysis p<sub>raw</sub> = 2.1x10<sup>-11</sup>.</p>", "links"=>[], "tags"=>["human", "26A", "candidate", "factor", "hypothyroid disease", "hypothyroidism risk locus", "CFA 12 Hypothyroidism", "Canine Hypothyroidism Identifies", "snp", "SRPK", "LHFPL", "dla", "haplotype", "Shared Major Risk Locus", "breed", "class II gene cluster", "dog leukocyte antigen", "slc"], "article_id"=>1508220, "categories"=>["Biological Sciences"], "users"=>["Matteo Bianchi", "Stina Dahlgren", "Jonathan Massey", "Elisabeth Dietschi", "Marcin Kierczak", "Martine Lund-Ziener", "Katarina Sundberg", "Stein Istre Thoresen", "Olle Kämpe", "Göran Andersson", "William E. R. Ollier", "Åke Hedhammar", "Tosso Leeb", "Kerstin Lindblad-Toh", "Lorna J. Kennedy", "Frode Lingaas", "Gerli Rosengren Pielberg"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0134720.g002", "stats"=>{"downloads"=>1, "page_views"=>30, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_A_Multi_Breed_Genome_Wide_Association_Analysis_for_Canine_Hypothyroidism_Identifies_a_Shared_Major_Risk_Locus_on_CFA12_Fig_2_/1508220", "title"=>"A Multi-Breed Genome-Wide Association Analysis for Canine Hypothyroidism Identifies a Shared Major Risk Locus on CFA12 - Fig 2", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-08-11 03:40:54"}
  • {"files"=>["https://ndownloader.figshare.com/files/2208803", "https://ndownloader.figshare.com/files/2208804", "https://ndownloader.figshare.com/files/2208805", "https://ndownloader.figshare.com/files/2208806"], "description"=>"<div><p>Hypothyroidism is a complex clinical condition found in both humans and dogs, thought to be caused by a combination of genetic and environmental factors. In this study we present a multi-breed analysis of predisposing genetic risk factors for hypothyroidism in dogs using three high-risk breeds—the Gordon Setter, Hovawart and the Rhodesian Ridgeback. Using a genome-wide association approach and meta-analysis, we identified a major hypothyroidism risk locus shared by these breeds on chromosome 12 (p = 2.1x10<sup>-11</sup>). Further characterisation of the candidate region revealed a shared ~167 kb risk haplotype (4,915,018–5,081,823 bp), tagged by two SNPs in almost complete linkage disequilibrium. This breed-shared risk haplotype includes three genes (<i>LHFPL5</i>, <i>SRPK1</i> and <i>SLC26A8</i>) and does not extend to the dog leukocyte antigen (DLA) class II gene cluster located in the vicinity. These three genes have not been identified as candidate genes for hypothyroid disease previously, but have functions that could potentially contribute to the development of the disease. Our results implicate the potential involvement of novel genes and pathways for the development of canine hypothyroidism, raising new possibilities for screening, breeding programmes and treatments in dogs. This study may also contribute to our understanding of the genetic etiology of human hypothyroid disease, which is one of the most common endocrine disorders in humans.</p></div>", "links"=>[], "tags"=>["human", "26A", "candidate", "factor", "hypothyroid disease", "hypothyroidism risk locus", "CFA 12 Hypothyroidism", "Canine Hypothyroidism Identifies", "snp", "SRPK", "LHFPL", "dla", "haplotype", "Shared Major Risk Locus", "breed", "class II gene cluster", "dog leukocyte antigen", "slc"], "article_id"=>1508229, "categories"=>["Biological Sciences"], "users"=>["Matteo Bianchi", "Stina Dahlgren", "Jonathan Massey", "Elisabeth Dietschi", "Marcin Kierczak", "Martine Lund-Ziener", "Katarina Sundberg", "Stein Istre Thoresen", "Olle Kämpe", "Göran Andersson", "William E. R. Ollier", "Åke Hedhammar", "Tosso Leeb", "Kerstin Lindblad-Toh", "Lorna J. Kennedy", "Frode Lingaas", "Gerli Rosengren Pielberg"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0134720.s001", "https://dx.doi.org/10.1371/journal.pone.0134720.s002", "https://dx.doi.org/10.1371/journal.pone.0134720.s003", "https://dx.doi.org/10.1371/journal.pone.0134720.s004"], "stats"=>{"downloads"=>3, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_A_Multi_Breed_Genome_Wide_Association_Analysis_for_Canine_Hypothyroidism_Identifies_a_Shared_Major_Risk_Locus_on_CFA12_/1508229", "title"=>"A Multi-Breed Genome-Wide Association Analysis for Canine Hypothyroidism Identifies a Shared Major Risk Locus on CFA12", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2015-08-11 03:40:54"}
  • {"files"=>["https://ndownloader.figshare.com/files/2208799"], "description"=>"<p>The upper panel indicates the alternative alleles in different grey shades, and the defined ~167 kb risk haplotype (4,915,018–5,081,823 bp) with red boundaries. Proportion of risk/non-risk haplotypes indicates the relative proportions of corresponding haplotypes among risk haplotypes determined in cases or non-risk haplotypes determined in controls, respectively. Star indicates a rare haplotype represented by only one chromosome. The lower panel shows the genomic location of the SNPs defining the risk haplotype in relation to protein coding genes (for each gene all the transcripts isoforms are included), CpG islands and conservation scores (figure adapted from: <a href=\"http://genome.ucsc.edu\" target=\"_blank\">http://genome.ucsc.edu</a>)</p>", "links"=>[], "tags"=>["human", "26A", "candidate", "factor", "hypothyroid disease", "hypothyroidism risk locus", "CFA 12 Hypothyroidism", "Canine Hypothyroidism Identifies", "snp", "SRPK", "LHFPL", "dla", "haplotype", "Shared Major Risk Locus", "breed", "class II gene cluster", "dog leukocyte antigen", "slc"], "article_id"=>1508225, "categories"=>["Biological Sciences"], "users"=>["Matteo Bianchi", "Stina Dahlgren", "Jonathan Massey", "Elisabeth Dietschi", "Marcin Kierczak", "Martine Lund-Ziener", "Katarina Sundberg", "Stein Istre Thoresen", "Olle Kämpe", "Göran Andersson", "William E. R. Ollier", "Åke Hedhammar", "Tosso Leeb", "Kerstin Lindblad-Toh", "Lorna J. Kennedy", "Frode Lingaas", "Gerli Rosengren Pielberg"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0134720.g005", "stats"=>{"downloads"=>1, "page_views"=>27, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Haplotype_analysis_from_all_breeds_identified_two_risk_haplotypes_in_cases_and_nine_non_risk_haplotypes_in_controls_/1508225", "title"=>"Haplotype analysis from all breeds identified two risk haplotypes in cases and nine non-risk haplotypes in controls.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-08-11 03:40:54"}

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{"start_date"=>"2015-01-01T00:00:00Z", "end_date"=>"2015-12-31T00:00:00Z", "subject_areas"=>[]}
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