Multiple Sclerosis Risk Variant HLA-DRB1*1501 Associates with High Expression of DRB1 Gene in Different Human Populations
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{"title"=>"Multiple sclerosis risk variant HLA-DRB1*1501 associates with high expression of DRB1 gene in different human populations", "type"=>"journal", "authors"=>[{"first_name"=>"Antonio", "last_name"=>"Alcina", "scopus_author_id"=>"6701389296"}, {"first_name"=>"Maríal Mar", "last_name"=>"de Abad-Grau", "scopus_author_id"=>"12809642500"}, {"first_name"=>"María", "last_name"=>"Fedetz", "scopus_author_id"=>"6508128367"}, {"first_name"=>"Guillermo", "last_name"=>"Izquierdo", "scopus_author_id"=>"7005179252"}, {"first_name"=>"Miguel", "last_name"=>"Lucas", "scopus_author_id"=>"7201860551"}, {"first_name"=>"Óscar", "last_name"=>"Fernández", "scopus_author_id"=>"7102560044"}, {"first_name"=>"Dorothy", "last_name"=>"Ndagire", "scopus_author_id"=>"24471995500"}, {"first_name"=>"Antonio", "last_name"=>"Catalá-Rabasa", "scopus_author_id"=>"36196192300"}, {"first_name"=>"Agustín", "last_name"=>"Ruiz", "scopus_author_id"=>"7203006899"}, {"first_name"=>"Javier", "last_name"=>"Gayán", "scopus_author_id"=>"55907979600"}, {"first_name"=>"Concepción", "last_name"=>"Delgado", "scopus_author_id"=>"23666833800"}, {"first_name"=>"Carmen", "last_name"=>"Arnal", "scopus_author_id"=>"57198383655"}, {"first_name"=>"Fuencisla", "last_name"=>"Matesanz", "scopus_author_id"=>"6603257781"}], "year"=>2012, "source"=>"PLoS ONE", "identifiers"=>{"pui"=>"364092930", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)", "issn"=>"19326203", "doi"=>"10.1371/journal.pone.0029819", "scopus"=>"2-s2.0-84855823921", "pmid"=>"22253788", "sgr"=>"84855823921"}, "id"=>"61133afc-ee49-37ea-8217-1cbd55567a66", "abstract"=>"The human leukocyte antigen (HLA) DRB1*1501 has been consistently associated with multiple sclerosis (MS) in nearly all populations tested. This points to a specific antigen presentation as the pathogenic mechanism though this does not fully explain the disease association. The identification of expression quantitative trait loci (eQTL) for genes in the HLA locus poses the question of the role of gene expression in MS susceptibility. We analyzed the eQTLs in the HLA region with respect to MS-associated HLA-variants obtained from genome-wide association studies (GWAS). We found that the Tag of DRB1*1501, rs3135388 A allele, correlated with high expression of DRB1, DRB5 and DQB1 genes in a Caucasian population. In quantitative terms, the MS-risk AA genotype carriers of rs3135388 were associated with 15.7-, 5.2- and 8.3-fold higher expression of DQB1, DRB5 and DRB1, respectively, than the non-risk GG carriers. The haplotype analysis of expression-associated variants in a Spanish MS cohort revealed that high expression of DRB1 and DQB1 alone did not contribute to the disease. However, in Caucasian, Asian and African American populations, the DRB1*1501 allele was always highly expressed. In other immune related diseases such as type 1 diabetes, inflammatory bowel disease, ulcerative colitis, asthma and IgA deficiency, the best GWAS-associated HLA SNPs were also eQTLs for different HLA Class II genes. Our data suggest that the DR/DQ expression levels, together with specific structural properties of alleles, seem to be the causal effect in MS and in other immunopathologies rather than specific antigen presentation alone.", "link"=>"http://www.mendeley.com/research/multiple-sclerosis-risk-variant-hladrb11501-associates-high-expression-drb1-gene-different-human-pop-8", "reader_count"=>77, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Professor > Associate Professor"=>1, "Researcher"=>15, "Student > Doctoral Student"=>5, "Student > Ph. D. Student"=>18, "Student > Postgraduate"=>2, "Student > Master"=>12, "Other"=>4, "Student > Bachelor"=>17, "Professor"=>2}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Professor > Associate Professor"=>1, "Researcher"=>15, "Student > Doctoral Student"=>5, "Student > Ph. D. Student"=>18, "Student > Postgraduate"=>2, "Student > Master"=>12, "Other"=>4, "Student > Bachelor"=>17, "Professor"=>2}, "reader_count_by_subject_area"=>{"Unspecified"=>5, "Biochemistry, Genetics and Molecular Biology"=>12, "Nursing and Health Professions"=>1, "Agricultural and Biological Sciences"=>25, "Medicine and Dentistry"=>20, "Neuroscience"=>5, "Pharmacology, Toxicology and Pharmaceutical Science"=>1, "Computer Science"=>2, "Immunology and Microbiology"=>5, "Veterinary Science and Veterinary Medicine"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>20}, "Neuroscience"=>{"Neuroscience"=>5}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>5}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>25}, "Computer Science"=>{"Computer Science"=>2}, "Nursing and Health Professions"=>{"Nursing and Health Professions"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>12}, "Unspecified"=>{"Unspecified"=>5}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>1}, "Veterinary Science and Veterinary Medicine"=>{"Veterinary Science and Veterinary Medicine"=>1}}, "reader_count_by_country"=>{"United States"=>1, "Brazil"=>2, "Mexico"=>1, "Germany"=>1, "Spain"=>1}, "group_count"=>3}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/693336"], "description"=>"<p>F_A, Frequency of affected; F_U Frequency of unaffected; OR , Odds Ratio; P, <i>P</i>-value of logistic regression analysis. Only haplotypes with higher frequency than 0.05 are shown. (>) stands for higher expression; (<) stands for lower expression. Data from African American are from McElroy et al. <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0029819#pone.0029819-McElroy2\" target=\"_blank\">[7]</a>. Haplotypes for African American are from rs9270986 (eQTL for <i>DRB5</i> and <i>DRB1</i> at the same time) and <i>DRB1*1501</i>.</p>", "links"=>[], "tags"=>["ms", "haplotypes", "bearing", "snps", "eqtls"], "article_id"=>363763, "categories"=>["Neuroscience", "Genetics", "Immunology"], "users"=>["Antonio Alcina", "María del Mar Abad-Grau", "Maria Fedetz", "Guillermo Izquierdo", "Miguel Lucas", "Oscar Fernández", "Dorothy Ndagire", "Antonio Catalá-Rabasa", "Agustín Ruiz", "Javier Gayán", "Concepción Delgado", "Carmen Arnal", "Fuencisla Matesanz"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0029819.t002", "stats"=>{"downloads"=>1, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Association_with_MS_of_the_haplotypes_bearing_the_DRB1_1501_SNPs_and_the_eQTLs_for_DRB5_DRB1_and_DQB1_genes_/363763", "title"=>"Association with MS of the haplotypes bearing the <i>DRB1*1501</i> SNPs and the eQTLs for <i>DRB5</i>, <i>DRB1</i> and <i>DQB1</i> genes.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2012-01-13 01:02:43"}
  • {"files"=>["https://ndownloader.figshare.com/files/352305", "https://ndownloader.figshare.com/files/352359"], "description"=>"<div><p>The human leukocyte antigen (HLA) <em>DRB1*1501</em> has been consistently associated with multiple sclerosis (MS) in nearly all populations tested. This points to a specific antigen presentation as the pathogenic mechanism though this does not fully explain the disease association. The identification of expression quantitative trait loci (eQTL) for genes in the HLA locus poses the question of the role of gene expression in MS susceptibility. We analyzed the eQTLs in the HLA region with respect to MS-associated HLA-variants obtained from genome-wide association studies (GWAS). We found that the Tag of <em>DRB1*1501</em>, rs3135388 A allele, correlated with high expression of <em>DRB1</em>, <em>DRB5</em> and <em>DQB1</em> genes in a Caucasian population. In quantitative terms, the MS-risk AA genotype carriers of rs3135388 were associated with 15.7-, 5.2- and 8.3-fold higher expression of <em>DQB1</em>, <em>DRB5</em> and <em>DRB1</em>, respectively, than the non-risk GG carriers. The haplotype analysis of expression-associated variants in a Spanish MS cohort revealed that high expression of <em>DRB1</em> and <em>DQB1</em> alone did not contribute to the disease. However, in Caucasian, Asian and African American populations, the <em>DRB1*1501</em> allele was always highly expressed. In other immune related diseases such as type 1 diabetes, inflammatory bowel disease, ulcerative colitis, asthma and IgA deficiency, the best GWAS-associated HLA SNPs were also eQTLs for different HLA Class II genes. Our data suggest that the <em>DR/DQ</em> expression levels, together with specific structural properties of alleles, seem to be the causal effect in MS and in other immunopathologies rather than specific antigen presentation alone.</p> </div>", "links"=>[], "tags"=>["sclerosis", "variant", "associates", "populations"], "article_id"=>129640, "categories"=>["Neuroscience", "Genetics", "Immunology"], "users"=>["Antonio Alcina", "María del Mar Abad-Grau", "Maria Fedetz", "Guillermo Izquierdo", "Miguel Lucas", "Oscar Fernández", "Dorothy Ndagire", "Antonio Catalá-Rabasa", "Agustín Ruiz", "Javier Gayán", "Concepción Delgado", "Carmen Arnal", "Fuencisla Matesanz"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0029819.s001", "https://dx.doi.org/10.1371/journal.pone.0029819.s002"], "stats"=>{"downloads"=>8, "page_views"=>14, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Multiple_Sclerosis_Risk_Variant_HLA_DRB1_1501_Associates_with_High_Expression_of_DRB1_Gene_in_Different_Human_Populations/129640", "title"=>"Multiple Sclerosis Risk Variant <em>HLA-DRB1*1501</em> Associates with High Expression of <em>DRB1</em> Gene in Different Human Populations", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2012-01-13 02:40:40"}
  • {"files"=>["https://ndownloader.figshare.com/files/692805"], "description"=>"<p>In all plots, expression levels are represented for the three genotype groups. (<b>A</b>) Box plots of expression data from normalized results of ILMN_1715169 (<i>DRB1</i>) probe generated by Illumina Human-6 v2 Expression BeadChip (EMBL-EBI database (<a href=\"http://www.ebi.ac.uk/arrayexpress/\" target=\"_blank\">http://www.ebi.ac.uk/arrayexpress/</a>) ID projects E-MTAB-198). (<b>B</b>) Box plot of expression data from the NM_002124 (<i>DRB1</i>) transcript of 41 CEU individuals obtained from RNA-Seq <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0029819#pone.0029819-Cheung1\" target=\"_blank\">[19]</a>. P-values are calculated by Kruskal Wallis Test.</p>", "links"=>[], "tags"=>["ms-risk", "variant", "rs9271100"], "article_id"=>363238, "categories"=>["Neuroscience", "Genetics", "Immunology"], "users"=>["Antonio Alcina", "María del Mar Abad-Grau", "Maria Fedetz", "Guillermo Izquierdo", "Miguel Lucas", "Oscar Fernández", "Dorothy Ndagire", "Antonio Catalá-Rabasa", "Agustín Ruiz", "Javier Gayán", "Concepción Delgado", "Carmen Arnal", "Fuencisla Matesanz"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0029819.g003", "stats"=>{"downloads"=>1, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Association_of_the_MS_risk_variant_rs9271100_with_DRB1_gene_expression_levels_/363238", "title"=>"Association of the MS-risk variant rs9271100 with <i>DRB1</i> gene expression levels.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-01-13 00:53:58"}
  • {"files"=>["https://ndownloader.figshare.com/files/692960"], "description"=>"<p>Expression data are from CEU individuals obtained from RNA-Seq <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0029819#pone.0029819-Caballero1\" target=\"_blank\">[9]</a>. The data are from the transcripts <i>DQB1</i> NM_002123, <i>DQA1</i> NM_002122, <i>DRB1</i> NM_002124, <i>DQA2</i> NM_020056 and <i>DRB5</i> NM_002125. Underlined are marked the risk alleles.</p>", "links"=>[], "tags"=>["risk-variants", "immune-related", "diseases", "levels", "hla"], "article_id"=>363389, "categories"=>["Neuroscience", "Genetics", "Immunology"], "users"=>["Antonio Alcina", "María del Mar Abad-Grau", "Maria Fedetz", "Guillermo Izquierdo", "Miguel Lucas", "Oscar Fernández", "Dorothy Ndagire", "Antonio Catalá-Rabasa", "Agustín Ruiz", "Javier Gayán", "Concepción Delgado", "Carmen Arnal", "Fuencisla Matesanz"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0029819.g004", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Association_of_risk_variants_for_different_immune_related_diseases_with_expression_levels_of_HLA_genes_/363389", "title"=>"Association of risk-variants for different immune-related diseases with expression levels of HLA genes.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-01-13 00:56:29"}
  • {"files"=>["https://ndownloader.figshare.com/files/693281"], "description"=>"<p>Diseases: Type 1 diabetes (T1D), inflammatory bowel disease (IBD), ulcerative colitis (UC), systemic lupus erythematosus (SLE), asthma, IgA deficiency and multiple sclerosis (MS). SNP GWAS indicate the most associated variant detected by GWAS, references in brackets. Transcripts are with Ensembl nomenclature. r values (correlation coefficient) and p-values from Spearman correlation test.</p>", "links"=>[], "tags"=>["hla", "variants", "diseases", "levels", "ii"], "article_id"=>363708, "categories"=>["Neuroscience", "Genetics", "Immunology"], "users"=>["Antonio Alcina", "María del Mar Abad-Grau", "Maria Fedetz", "Guillermo Izquierdo", "Miguel Lucas", "Oscar Fernández", "Dorothy Ndagire", "Antonio Catalá-Rabasa", "Agustín Ruiz", "Javier Gayán", "Concepción Delgado", "Carmen Arnal", "Fuencisla Matesanz"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0029819.t003", "stats"=>{"downloads"=>0, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Most_associated_HLA_variants_of_different_diseases_and_correlation_with_expression_levels_of_HLA_Class_II_genes_/363708", "title"=>"Most associated HLA variants of different diseases and correlation with expression levels of HLA Class II genes.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2012-01-13 01:01:48"}
  • {"files"=>["https://ndownloader.figshare.com/files/692535"], "description"=>"<p>The figure shows the strength of association between SNPs and gene expression levels, plotted as −log <i>P</i>-values. Coordinates are in NCBI Build 36. Shown are the CEU, YRI, LWK, MEX, GHI, CHB and JPT HapMap populations <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0029819#pone.0029819-International1\" target=\"_blank\">[26]</a>.</p>", "links"=>[], "tags"=>["hapmap", "iii", "snps", "hla", "levels"], "article_id"=>362968, "categories"=>["Neuroscience", "Genetics", "Immunology"], "users"=>["Antonio Alcina", "María del Mar Abad-Grau", "Maria Fedetz", "Guillermo Izquierdo", "Miguel Lucas", "Oscar Fernández", "Dorothy Ndagire", "Antonio Catalá-Rabasa", "Agustín Ruiz", "Javier Gayán", "Concepción Delgado", "Carmen Arnal", "Fuencisla Matesanz"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0029819.g001", "stats"=>{"downloads"=>3, "page_views"=>12, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Association_of_HapMap_III_SNPs_from_the_HLA_region_with_expression_levels_of_the_HLA_DRB1_gene_/362968", "title"=>"Association of HapMap III SNPs from the HLA region with expression levels of the HLA <i>DRB1</i> gene.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-01-13 00:49:28"}
  • {"files"=>["https://ndownloader.figshare.com/files/692693"], "description"=>"<p>Image from the UCSC browser showing the HLA Class II region. Vertical bars indicate the location of eQTLs (0.0001 permutation threshold) from all populations. Vertical red bars indicate the common eQTLs among all populations studied.</p>", "links"=>[], "tags"=>["snps"], "article_id"=>363123, "categories"=>["Neuroscience", "Genetics", "Immunology"], "users"=>["Antonio Alcina", "María del Mar Abad-Grau", "Maria Fedetz", "Guillermo Izquierdo", "Miguel Lucas", "Oscar Fernández", "Dorothy Ndagire", "Antonio Catalá-Rabasa", "Agustín Ruiz", "Javier Gayán", "Concepción Delgado", "Carmen Arnal", "Fuencisla Matesanz"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0029819.g002", "stats"=>{"downloads"=>1, "page_views"=>10, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Location_of_SNPs_associated_with_DRB1_gene_expression_in_the_different_human_populations_/363123", "title"=>"Location of SNPs associated with <i>DRB1</i> gene expression in the different human populations.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-01-13 00:52:03"}
  • {"files"=>["https://ndownloader.figshare.com/files/693234"], "description"=>"<p>F_A, Frequency of affected; F_U, Frequency of unaffected; NA, not applicable; <i>P</i> cond, <i>P</i>-value of logistic regression analysis conditioned on the respective SNP; <i>OR</i>, odds ratio; <i>SNP</i>, single-nucleotide polymorphism. The data from African American are from McElroy et al. <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0029819#pone.0029819-McElroy2\" target=\"_blank\">[7]</a>.</p>", "links"=>[], "tags"=>["logistic", "regression", "ms"], "article_id"=>363666, "categories"=>["Neuroscience", "Genetics", "Immunology"], "users"=>["Antonio Alcina", "María del Mar Abad-Grau", "Maria Fedetz", "Guillermo Izquierdo", "Miguel Lucas", "Oscar Fernández", "Dorothy Ndagire", "Antonio Catalá-Rabasa", "Agustín Ruiz", "Javier Gayán", "Concepción Delgado", "Carmen Arnal", "Fuencisla Matesanz"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0029819.t001", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Conditional_logistic_regression_analysis_of_the_MS_associated_variants_/363666", "title"=>"Conditional logistic regression analysis of the MS associated variants.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2012-01-13 01:01:06"}
  • {"files"=>["https://ndownloader.figshare.com/files/693116"], "description"=>"<p>Data are from HapMap III CEU population. (<b>A</b>) Linkage disequilibrium by r<sup>2</sup>. (<b>B</b>) Linkage disequilibrium by D′. Disease abbreviations: Type 1 diabetes (T1D), inflammatory bowel disease (IBD), ulcerative colitis (UC), systemic lupus erythematosus (SLE), asthma and IgA deficiency.</p>", "links"=>[], "tags"=>["plots", "gwas-", "snps"], "article_id"=>363551, "categories"=>["Neuroscience", "Genetics", "Immunology"], "users"=>["Antonio Alcina", "María del Mar Abad-Grau", "Maria Fedetz", "Guillermo Izquierdo", "Miguel Lucas", "Oscar Fernández", "Dorothy Ndagire", "Antonio Catalá-Rabasa", "Agustín Ruiz", "Javier Gayán", "Concepción Delgado", "Carmen Arnal", "Fuencisla Matesanz"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0029819.g005", "stats"=>{"downloads"=>1, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_LD_plots_of_the_GWAS_SNPs_associated_with_different_immune_related_disease_/363551", "title"=>"LD plots of the GWAS- SNPs associated with different immune related disease.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-01-13 00:59:11"}

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