Fine-Mapping the Genetic Association of the Major Histocompatibility Complex in Multiple Sclerosis: HLA and Non-HLA Effects
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{"title"=>"Fine-Mapping the Genetic Association of the Major Histocompatibility Complex in Multiple Sclerosis: HLA and Non-HLA Effects", "type"=>"journal", "authors"=>[{"first_name"=>"Nikolaos A.", "last_name"=>"Patsopoulos", "scopus_author_id"=>"8526988800"}, {"first_name"=>"Lisa F.", "last_name"=>"Barcellos", "scopus_author_id"=>"13605440300"}, {"first_name"=>"Rogier Q.", "last_name"=>"Hintzen", "scopus_author_id"=>"26643157200"}, {"first_name"=>"Catherine", "last_name"=>"Schaefer", "scopus_author_id"=>"7202212082"}, {"first_name"=>"Cornelia M.", "last_name"=>"van Duijn", "scopus_author_id"=>"36037246700"}, {"first_name"=>"Janelle A.", "last_name"=>"Noble", "scopus_author_id"=>"35425452800"}, {"first_name"=>"Towfique", "last_name"=>"Raj", "scopus_author_id"=>"39561540100"}, {"first_name"=>"Pierre Antoine", "last_name"=>"Gourraud", "scopus_author_id"=>"6506489910"}, {"first_name"=>"Barbara E.", "last_name"=>"Stranger", "scopus_author_id"=>"6507901873"}, {"first_name"=>"Jorge", "last_name"=>"Oksenberg", "scopus_author_id"=>"7005749242"}, {"first_name"=>"Tomas", "last_name"=>"Olsson", "scopus_author_id"=>"55550356500"}, {"first_name"=>"Bruce V.", "last_name"=>"Taylor", "scopus_author_id"=>"7403035814"}, {"first_name"=>"Stephen", "last_name"=>"Sawcer", "scopus_author_id"=>"7003722155"}, {"first_name"=>"David A.", "last_name"=>"Hafler", "scopus_author_id"=>"7101602133"}, {"first_name"=>"Mary", "last_name"=>"Carrington", "scopus_author_id"=>"7102278850"}, {"first_name"=>"Philip L.", "last_name"=>"De Jager", "scopus_author_id"=>"7005494360"}, {"first_name"=>"Paul I.W.", "last_name"=>"de Bakker", "scopus_author_id"=>"6701510692"}], "year"=>2013, "source"=>"PLoS Genetics", "identifiers"=>{"issn"=>"15537390", "scopus"=>"2-s2.0-84888231843", "sgr"=>"84888231843", "pui"=>"370341785", "isbn"=>"1553-7404 (Electronic)\\r1553-7390 (Linking)", "pmid"=>"24278027", "doi"=>"10.1371/journal.pgen.1003926"}, "id"=>"cbc9faf0-fd75-3521-99b5-68474cd0feae", "abstract"=>"The major histocompatibility complex (MHC) region is strongly associated with multiple sclerosis (MS) susceptibility. 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This study dissects the independent effects in the MHC, a critical region for MS susceptibility that harbors multiple risk alleles.", "link"=>"http://www.mendeley.com/research/finemapping-genetic-association-major-histocompatibility-complex-multiple-sclerosis-hla-nonhla-effec", "reader_count"=>141, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Professor > Associate Professor"=>4, "Librarian"=>1, "Researcher"=>39, "Student > Doctoral Student"=>13, "Student > Ph. D. Student"=>33, "Student > Postgraduate"=>6, "Student > Master"=>17, "Other"=>6, "Student > Bachelor"=>17, "Professor"=>4}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Professor > Associate Professor"=>4, "Librarian"=>1, "Researcher"=>39, "Student > Doctoral Student"=>13, "Student > Ph. D. 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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1291642"], "description"=>"<p>IMSGC: International Multiple Sclerosis Genetics Consortium; BWH: Brigham & Women's Hospital; ANZ: Australia and New Zealand genetic study; DU: Netherlands; US: United States; SW: Switzerland.</p>", "links"=>[], "tags"=>[], "article_id"=>859339, "categories"=>["Biological Sciences"], "users"=>["Nikolaos A. Patsopoulos", "Lisa F. Barcellos", "Rogier Q. Hintzen", "Catherine Schaefer", "Cornelia M. van Duijn", "Janelle A. Noble", "Towfique Raj", "Pierre-Antoine Gourraud", "Barbara E. Stranger", "Jorge Oksenberg", "Tomas Olsson", "Bruce V. Taylor", "Stephen Sawcer", "David A. Hafler", "Mary Carrington", "Philip L. De Jager", "Paul I. W. de Bakker"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1003926.t001", "stats"=>{"downloads"=>1, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Descriptive_characteristic_of_analyzed_data_sets_/859339", "title"=>"Descriptive characteristic of analyzed data sets.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-11-21 03:27:45"}
  • {"files"=>["https://ndownloader.figshare.com/files/1291634"], "description"=>"<p>Panels on the left are regional association plots for all variants in the MHC region; each diamond is a polymorphism evaluated in the analysis (SNP, HLA type, amino acid). The index variant that best captures the effect of each locus is highlighted with a larger diamond. Variants that are in LD with the index variant are colored, with the intensity of the color being proportional to the extent of LD. The panels on the right plot the −log<sub>10</sub>(p-value) of the eight analyzed HLA genes. The order of the genes is based on their position on chromosome 6. The rows represent univariate analysis (A, B), conditioning on six <i>HLA-DRB1</i> alleles (*15:01, *03:01, *13:03, *04:04, *04:01, and *14:01) (C, D), conditioning on the above and HLA-A*02:01 (E, F), conditioning on the above and the <i>DPB1</i> effect (G, H), conditioning on the above and rs2516489 (I, J), conditioning on the above and <i>B*37:01</i> (K, L), conditioning on the above and <i>B*38:01</i> (M, N). In panels M and N the solid black line marks the threshold of statistical significance in the study.</p>", "links"=>[], "tags"=>["variants", "hla"], "article_id"=>859331, "categories"=>["Biological Sciences"], "users"=>["Nikolaos A. Patsopoulos", "Lisa F. Barcellos", "Rogier Q. Hintzen", "Catherine Schaefer", "Cornelia M. van Duijn", "Janelle A. Noble", "Towfique Raj", "Pierre-Antoine Gourraud", "Barbara E. Stranger", "Jorge Oksenberg", "Tomas Olsson", "Bruce V. Taylor", "Stephen Sawcer", "David A. Hafler", "Mary Carrington", "Philip L. De Jager", "Paul I. W. de Bakker"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1003926.g001", "stats"=>{"downloads"=>1, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Association_plots_for_the_analyzed_variants_and_HLA_genes_/859331", "title"=>"Association plots for the analyzed variants and HLA genes.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-11-21 03:27:45"}
  • {"files"=>["https://ndownloader.figshare.com/files/1291648", "https://ndownloader.figshare.com/files/1291649", "https://ndownloader.figshare.com/files/1291650", "https://ndownloader.figshare.com/files/1291651", "https://ndownloader.figshare.com/files/1291652", "https://ndownloader.figshare.com/files/1291653", "https://ndownloader.figshare.com/files/1291654", "https://ndownloader.figshare.com/files/1291655", "https://ndownloader.figshare.com/files/1291656", "https://ndownloader.figshare.com/files/1291657"], "description"=>"<div><p>The major histocompatibility complex (MHC) region is strongly associated with multiple sclerosis (MS) susceptibility. <i>HLA</i>-<i>DRB1*15:01</i> has the strongest effect, and several other alleles have been reported at different levels of validation. Using SNP data from genome-wide studies, we imputed and tested classical alleles and amino acid polymorphisms in 8 classical human leukocyte antigen (HLA) genes in 5,091 cases and 9,595 controls. We identified 11 statistically independent effects overall: 6 <i>HLA-DRB1</i> and one <i>DPB1</i> alleles in class II, one <i>HLA-A</i> and two <i>B</i> alleles in class I, and one signal in a region spanning from <i>MICB</i> to <i>LST1</i>. This genomic segment does not contain any HLA class I or II genes and provides robust evidence for the involvement of a non-HLA risk allele within the MHC. Interestingly, this region contains the <i>TNF</i> gene, the cognate ligand of the well-validated <i>TNFRSF1A</i> MS susceptibility gene. The classical HLA effects can be explained to some extent by polymorphic amino acid positions in the peptide-binding grooves. This study dissects the independent effects in the MHC, a critical region for MS susceptibility that harbors multiple risk alleles.</p></div>", "links"=>[], "tags"=>["histocompatibility", "hla", "non-hla"], "article_id"=>859345, "categories"=>["Biological Sciences"], "users"=>["Nikolaos A. Patsopoulos", "Lisa F. Barcellos", "Rogier Q. Hintzen", "Catherine Schaefer", "Cornelia M. van Duijn", "Janelle A. Noble", "Towfique Raj", "Pierre-Antoine Gourraud", "Barbara E. Stranger", "Jorge Oksenberg", "Tomas Olsson", "Bruce V. Taylor", "Stephen Sawcer", "David A. Hafler", "Mary Carrington", "Philip L. De Jager", "Paul I. W. de Bakker"], "doi"=>["https://dx.doi.org/10.1371/journal.pgen.1003926.s001", "https://dx.doi.org/10.1371/journal.pgen.1003926.s002", "https://dx.doi.org/10.1371/journal.pgen.1003926.s003", "https://dx.doi.org/10.1371/journal.pgen.1003926.s004", "https://dx.doi.org/10.1371/journal.pgen.1003926.s005", "https://dx.doi.org/10.1371/journal.pgen.1003926.s006", "https://dx.doi.org/10.1371/journal.pgen.1003926.s007", "https://dx.doi.org/10.1371/journal.pgen.1003926.s008", "https://dx.doi.org/10.1371/journal.pgen.1003926.s009", "https://dx.doi.org/10.1371/journal.pgen.1003926.s010"], "stats"=>{"downloads"=>31, "page_views"=>14, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Fine_Mapping_the_Genetic_Association_of_the_Major_Histocompatibility_Complex_in_Multiple_Sclerosis_HLA_and_Non_HLA_Effects_/859345", "title"=>"Fine-Mapping the Genetic Association of the Major Histocompatibility Complex in Multiple Sclerosis: HLA and Non-HLA Effects", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2013-11-21 03:27:45"}
  • {"files"=>["https://ndownloader.figshare.com/files/1291641"], "description"=>"<p>The first 6 rows are H3K4me3 (green) data for CD4 memory primary cells, CD4 naïve primary cells, CD8 memory primary cells, CD8 naïve primary cells, Treg primary cells, and GM12878 cell line (B-lymphocyte, lymphoblastoid, International HapMap Project - CEPH/Utah - European Caucasion, Epstein-Barr Virus). The next 5 rows display H3K27ac (blue) data for CD4 memory primary cells, CD4 naïve primary cells, CD8 memory primary cells, CD8 naïve primary cells, and GM12878 cell line, respectively. Then there are the H3K36me3 (green) data for CD4 memory primary cells, CD4 naïve primary cells, CD8 memory primary cells, CD8 naïve primary cells, Treg primary cells, and GM12878 cell line. The chomatin states displayed are for CD4 memory primary cells, CD4 naïve primary cells, CD8 memory primary cells, CD8 naïve primary cells, and GM12878 cell line. The DNase hypersensitivity sites are for CD4 primary cells, CD8 primary cells, CD14+ monocytes, Treg, Th1, Th2, Th17 and GM12878 cell line, respectively. The detailed colorscheme of the chromatin states is listed in the Supplementary material. Briefly, red corresponds to transcription start sites (TSSs) and/or active promoters, orange/yellow to enhancers, green to transcription, and white/grey to heterochromain. All data are publicly available data from ENCODE and NIH Roadmap. The last row displays the −log10(p) of the SNPs in the LD block after adjustment with the <i>HLA-DRB1*15:01</i> effect.</p>", "links"=>[], "tags"=>["annotation"], "article_id"=>859338, "categories"=>["Biological Sciences"], "users"=>["Nikolaos A. Patsopoulos", "Lisa F. Barcellos", "Rogier Q. Hintzen", "Catherine Schaefer", "Cornelia M. van Duijn", "Janelle A. Noble", "Towfique Raj", "Pierre-Antoine Gourraud", "Barbara E. Stranger", "Jorge Oksenberg", "Tomas Olsson", "Bruce V. Taylor", "Stephen Sawcer", "David A. Hafler", "Mary Carrington", "Philip L. De Jager", "Paul I. W. de Bakker"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1003926.g003", "stats"=>{"downloads"=>0, "page_views"=>12, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Functional_annotation_of_the_MICB_LST1_/859338", "title"=>"Functional annotation of the <i>MICB-LST1</i>.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-11-21 03:27:45"}
  • {"files"=>["https://ndownloader.figshare.com/files/1291638"], "description"=>"<p>All structures are positioned to accommodate the view of the peptide-binding groove and the associated amino acid residues. The Protein Data Bank entries 3pdo, 1a1m, 3lqz, and 2bvp were used to produce the 3D structures, respectively, using UCSF Chimera <a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003926#pgen.1003926-Pettersen1\" target=\"_blank\">[49]</a>.</p>", "links"=>[], "tags"=>["hla", "dp"], "article_id"=>859335, "categories"=>["Biological Sciences"], "users"=>["Nikolaos A. Patsopoulos", "Lisa F. Barcellos", "Rogier Q. Hintzen", "Catherine Schaefer", "Cornelia M. van Duijn", "Janelle A. Noble", "Towfique Raj", "Pierre-Antoine Gourraud", "Barbara E. Stranger", "Jorge Oksenberg", "Tomas Olsson", "Bruce V. Taylor", "Stephen Sawcer", "David A. Hafler", "Mary Carrington", "Philip L. De Jager", "Paul I. W. de Bakker"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1003926.g002", "stats"=>{"downloads"=>2, "page_views"=>13, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_3D_ribbon_models_for_HLA_DR_HLA_A_HLA_DP_and_HLA_B_/859335", "title"=>"3D ribbon models for HLA DR, HLA A, HLA DP and HLA B.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-11-21 03:27:45"}

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Relative Metric

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