Trans-Ancestral Studies Fine Map the SLE-Susceptibility Locus TNFSF4
Publication Date
July 18, 2013
Journal
PLOS Genetics
Authors
Harinder Manku, Carl D. Langefeld, Sandra G. Guerra, Talat H. Malik, et al
Volume
9
Issue
7
Pages
e1003554
DOI
https://dx.plos.org/10.1371/journal.pgen.1003554
Publisher URL
http://journals.plos.org/plosgenetics/article?id=10.1371%2Fjournal.pgen.1003554
PubMed
http://www.ncbi.nlm.nih.gov/pubmed/23874208
PubMed Central
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3715547
Europe PMC
http://europepmc.org/abstract/MED/23874208
Web of Science
000322321100002
Scopus
84880772196
Mendeley
http://www.mendeley.com/research/transancestral-studies-fine-map-slesusceptibility-locus-tnfsf4
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Mendeley | Further Information

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Hal", "last_name"=>"Scofield", "scopus_author_id"=>"7005409257"}, {"first_name"=>"Nan", "last_name"=>"Shen", "scopus_author_id"=>"7102785475"}, {"first_name"=>"Anne M.", "last_name"=>"Stevens", "scopus_author_id"=>"7202107377"}, {"first_name"=>"Celi", "last_name"=>"Sun", "scopus_author_id"=>"36184759700"}, {"first_name"=>"Gary S.", "last_name"=>"Gilkeson", "scopus_author_id"=>"7005802718"}, {"first_name"=>"Jeff C.", "last_name"=>"Edberg", "scopus_author_id"=>"7005968167"}, {"first_name"=>"Robert P.", "last_name"=>"Kimberly", "scopus_author_id"=>"7005738540"}, {"first_name"=>"Swapan K.", "last_name"=>"Nath", "scopus_author_id"=>"7102759611"}, {"first_name"=>"Betty P.", "last_name"=>"Tsao", "scopus_author_id"=>"7005956550"}, {"first_name"=>"Tim J.", "last_name"=>"Vyse", "scopus_author_id"=>"7003955999"}], "year"=>2013, "source"=>"PLoS Genetics", "identifiers"=>{"scopus"=>"2-s2.0-84880772196", "sgr"=>"84880772196", "issn"=>"15537390", "doi"=>"10.1371/journal.pgen.1003554", "pmid"=>"23874208", "isbn"=>"1553-7404 (Electronic)\\r1553-7390 (Linking)", "pui"=>"369438582"}, "id"=>"34be4c46-4db7-3e98-aad7-7f25d5960166", "abstract"=>"We previously established an 80 kb haplotype upstream of TNFSF4 as a susceptibility locus in the autoimmune disease SLE. SLE-associated alleles at this locus are associated with inflammatory disorders, including atherosclerosis and ischaemic stroke. In Europeans, the TNFSF4 causal variants have remained elusive due to strong linkage disequilibrium exhibited by alleles spanning the region. Using a trans-ancestral approach to fine-map the locus, utilising 17,900 SLE and control subjects including Amerindian/Hispanics (1348 cases, 717 controls), African-Americans (AA) (1529, 2048) and better powered cohorts of Europeans and East Asians, we find strong association of risk alleles in all ethnicities; the AA association replicates in African-American Gullah (152,122). The best evidence of association comes from two adjacent markers: rs2205960-T (P=1.71 × 10(-34) , OR=1.43[1.26-1.60]) and rs1234317-T (P=1.16 × 10(-28) , OR=1.38[1.24-1.54]). Inference of fine-scale recombination rates for all populations tested finds the 80 kb risk and non-risk haplotypes in all except African-Americans. In this population the decay of recombination equates to an 11 kb risk haplotype, anchored in the 5' region proximal to TNFSF4 and tagged by rs2205960-T after 1000 Genomes phase 1 (v3) imputation. Conditional regression analyses delineate the 5' risk signal to rs2205960-T and the independent non-risk signal to rs1234314-C. Our case-only and SLE-control cohorts demonstrate robust association of rs2205960-T with autoantibody production. The rs2205960-T is predicted to form part of a decameric motif which binds NF-κBp65 with increased affinity compared to rs2205960-G. ChIP-seq data also indicate NF-κB interaction with the DNA sequence at this position in LCL cells. Our research suggests association of rs2205960-T with SLE across multiple groups and an independent non-risk signal at rs1234314-C. rs2205960-T is associated with autoantibody production and lymphopenia. Our data confirm a global signal at TNFSF4 and a role for the expressed product at multiple stages of lymphocyte dysregulation during SLE pathogenesis. We confirm the validity of trans-ancestral mapping in a complex trait.", "link"=>"http://www.mendeley.com/research/transancestral-studies-fine-map-slesusceptibility-locus-tnfsf4", "reader_count"=>43, "reader_count_by_academic_status"=>{"Unspecified"=>3, "Professor > Associate Professor"=>1, "Researcher"=>12, "Student > Ph. D. Student"=>15, "Other"=>3, "Student > Master"=>3, "Student > Bachelor"=>4, "Professor"=>2}, "reader_count_by_user_role"=>{"Unspecified"=>3, "Professor > Associate Professor"=>1, "Researcher"=>12, "Student > Ph. D. Student"=>15, "Other"=>3, "Student > Master"=>3, "Student > Bachelor"=>4, "Professor"=>2}, "reader_count_by_subject_area"=>{"Engineering"=>1, "Unspecified"=>3, "Biochemistry, Genetics and Molecular Biology"=>4, "Agricultural and Biological Sciences"=>14, "Medicine and Dentistry"=>15, "Pharmacology, Toxicology and Pharmaceutical Science"=>1, "Physics and Astronomy"=>1, "Social Sciences"=>1, "Immunology and Microbiology"=>3}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>1}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>15}, "Social Sciences"=>{"Social Sciences"=>1}, "Physics and Astronomy"=>{"Physics and Astronomy"=>1}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>3}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>14}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>4}, "Unspecified"=>{"Unspecified"=>3}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>1}}, "reader_count_by_country"=>{"Netherlands"=>1, "United Kingdom"=>1, "Mexico"=>1}, "group_count"=>2}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1121880"], "description"=>"<p>The strength of the association (-log10uncorrected<i>P</i>) of markers across 240 kb of chromosome 1q25. This regional plot depicts <i>TNFSF4</i> association with SLE versus chromosomal position (kb) in East Asians, Europeans, Hispanics and African-American populations. The most associated variants in each group are labelled, as is the best-associated meta-analysis SNP <i>rs2205960</i>. Markers are colour-coded for their correlation coefficient (r<sup>2</sup>) values according to the legend.</p>", "links"=>[], "tags"=>["genetics", "Genetics of disease", "Human genetics", "Molecular genetics", "population genetics", "immunology", "Genetics of the immune system", "locus", "african-american", "sle-control"], "article_id"=>747873, "categories"=>["Biological Sciences"], "users"=>["Harinder Manku", "Carl D. Langefeld", "Sandra G. Guerra", "Talat H. Malik", "Marta Alarcon-Riquelme", "Juan-Manuel Anaya", "Sang-Cheol Bae", "Susan A. Boackle", "Elizabeth E. Brown", "Lindsey A. Criswell", "Barry I. Freedman", "Patrick M. Gaffney", "Peter A. Gregersen", "Joel M. Guthridge", "Sang-Hoon Han", "John B. Harley", "Chaim O. Jacob", "Judith A. James", "Diane L. Kamen", "Kenneth M. Kaufman", "Jennifer A. Kelly", "Javier Martin", "Joan T. Merrill", "Kathy L. Moser", "Timothy B. Niewold", "So-Yeon Park", "Bernardo A. Pons-Estel", "Amr H. Sawalha", "R. Hal Scofield", "Nan Shen", "Anne M. Stevens", "Celi Sun", "Gary S. Gilkeson", "Jeff C. Edberg", "Robert P. Kimberly", "Swapan K. Nath", "Betty P. Tsao", "Tim J. Vyse"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1003554.g002", "stats"=>{"downloads"=>1, "page_views"=>13, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Single_marker_association_at_TNFSF4_locus_in_A_East_Asian_B_European_C_Hispanic_D_African_American_SLE_control_populations_/747873", "title"=>"Single marker association at <i>TNFSF4</i> locus in <i>A</i>. East Asian, <i>B</i>. European, <i>C</i>. Hispanic, <i>D</i>. African-American SLE-control populations.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-07-18 02:09:50"}
  • {"files"=>["https://ndownloader.figshare.com/files/1121883"], "description"=>"<p>This section of chromosome 1q25.1 encompasses the <i>TNFSF4</i> gene and upstream region as defined by custom algorithm in Haploview 4.2. The measure of LD was used to depict 57 SNPs common to all cohorts, post QC and 1000 genomes imputation. The pair-wise correlations between <i>TNFSF4</i> markers is illustrated in these plots by the correlation coefficient R<sup>2</sup>(where r<sup>2</sup> = 0 = no correlation, white; 02<1, gradations of grey; R<sup>2</sup> = 1 = complete correlation, black). The <i>TNFSF4</i> gene is positioned above the plots relative to haplotype blocks (black triangles) and grey ticks indicate SNP locations to scale.</p>", "links"=>[], "tags"=>["genetics", "Genetics of disease", "Human genetics", "Molecular genetics", "population genetics", "immunology", "Genetics of the immune system", "locus"], "article_id"=>747876, "categories"=>["Biological Sciences"], "users"=>["Harinder Manku", "Carl D. Langefeld", "Sandra G. Guerra", "Talat H. Malik", "Marta Alarcon-Riquelme", "Juan-Manuel Anaya", "Sang-Cheol Bae", "Susan A. Boackle", "Elizabeth E. Brown", "Lindsey A. Criswell", "Barry I. Freedman", "Patrick M. Gaffney", "Peter A. Gregersen", "Joel M. Guthridge", "Sang-Hoon Han", "John B. Harley", "Chaim O. Jacob", "Judith A. James", "Diane L. Kamen", "Kenneth M. Kaufman", "Jennifer A. Kelly", "Javier Martin", "Joan T. Merrill", "Kathy L. Moser", "Timothy B. Niewold", "So-Yeon Park", "Bernardo A. Pons-Estel", "Amr H. Sawalha", "R. Hal Scofield", "Nan Shen", "Anne M. Stevens", "Celi Sun", "Gary S. Gilkeson", "Jeff C. Edberg", "Robert P. Kimberly", "Swapan K. Nath", "Betty P. Tsao", "Tim J. Vyse"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1003554.g003", "stats"=>{"downloads"=>2, "page_views"=>13, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_LD_plots_at_TNFSF4_locus_in_four_populations_/747876", "title"=>"LD plots at <i>TNFSF4</i> locus in four populations.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-07-18 02:09:50"}
  • {"files"=>["https://ndownloader.figshare.com/files/1121888"], "description"=>"<p>Plots are constructed using phased haplotypes for a. <i>East Asians</i>, b. <i>Europeans</i>, c. <i>Hispanics</i> and d. <i>African-Americans</i> and illustrate breakdown of LD with increasing distances from a core proximal <i>TNFSF4</i> SNP and are approximately to scale. The core is located at the <i>TNFSF4</i> gene-5′ boundary (black circle) and is selected as the most proximal 5′ marker, <i>rs1234314</i>, in each population. Gene location is depicted to scale; we have additionally labelled each plot to show the location of <i>rs1234317</i> and <i>rs2205960</i>, the best-associated markers from the meta-analysis.</p>", "links"=>[], "tags"=>["genetics", "Genetics of disease", "Human genetics", "Molecular genetics", "population genetics", "immunology", "Genetics of the immune system", "bifurcation", "diagrams"], "article_id"=>747881, "categories"=>["Biological Sciences"], "users"=>["Harinder Manku", "Carl D. Langefeld", "Sandra G. Guerra", "Talat H. Malik", "Marta Alarcon-Riquelme", "Juan-Manuel Anaya", "Sang-Cheol Bae", "Susan A. Boackle", "Elizabeth E. Brown", "Lindsey A. Criswell", "Barry I. Freedman", "Patrick M. Gaffney", "Peter A. Gregersen", "Joel M. Guthridge", "Sang-Hoon Han", "John B. Harley", "Chaim O. Jacob", "Judith A. James", "Diane L. Kamen", "Kenneth M. Kaufman", "Jennifer A. Kelly", "Javier Martin", "Joan T. Merrill", "Kathy L. Moser", "Timothy B. Niewold", "So-Yeon Park", "Bernardo A. Pons-Estel", "Amr H. Sawalha", "R. Hal Scofield", "Nan Shen", "Anne M. Stevens", "Celi Sun", "Gary S. Gilkeson", "Jeff C. Edberg", "Robert P. Kimberly", "Swapan K. Nath", "Betty P. Tsao", "Tim J. Vyse"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1003554.g004", "stats"=>{"downloads"=>13, "page_views"=>50, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Haplotype_Bifurcation_Diagrams_of_TNFSF4_risk_and_TNFSF4_non_risk_for_Four_Populations_/747881", "title"=>"Haplotype Bifurcation Diagrams of <i>TNFSF4<sub>risk</sub></i> and <i>TNFSF4<sub>non-</sub></i><sub><b>risk</b></sub> for Four Populations.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-07-18 02:09:50"}
  • {"files"=>["https://ndownloader.figshare.com/files/1121889"], "description"=>"<p>5′ RACE analysis was used to map the <i>TNFSF4</i> transcription start site. Three out of four putative splice variants modelled by the Aceview tool in the UCSC genome browser were validated in a European individual. Splice variants a. and b. are protein coding, whilst variant c. is transcribed but not translated.</p>", "links"=>[], "tags"=>["genetics", "Genetics of disease", "Human genetics", "Molecular genetics", "population genetics", "immunology", "Genetics of the immune system", "splice"], "article_id"=>747882, "categories"=>["Biological Sciences"], "users"=>["Harinder Manku", "Carl D. Langefeld", "Sandra G. Guerra", "Talat H. Malik", "Marta Alarcon-Riquelme", "Juan-Manuel Anaya", "Sang-Cheol Bae", "Susan A. Boackle", "Elizabeth E. Brown", "Lindsey A. Criswell", "Barry I. Freedman", "Patrick M. Gaffney", "Peter A. Gregersen", "Joel M. Guthridge", "Sang-Hoon Han", "John B. Harley", "Chaim O. Jacob", "Judith A. James", "Diane L. Kamen", "Kenneth M. Kaufman", "Jennifer A. Kelly", "Javier Martin", "Joan T. Merrill", "Kathy L. Moser", "Timothy B. Niewold", "So-Yeon Park", "Bernardo A. Pons-Estel", "Amr H. Sawalha", "R. Hal Scofield", "Nan Shen", "Anne M. Stevens", "Celi Sun", "Gary S. Gilkeson", "Jeff C. Edberg", "Robert P. Kimberly", "Swapan K. Nath", "Betty P. Tsao", "Tim J. Vyse"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1003554.g005", "stats"=>{"downloads"=>1, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Confirmation_of_TNFSF4_start_site_and_splice_variants_/747882", "title"=>"Confirmation of <i>TNFSF4</i> start site and splice variants.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-07-18 02:09:50"}
  • {"files"=>["https://ndownloader.figshare.com/files/1121892"], "description"=>"<p><i>A</i>. Degeneracy within the core 10-base motif is illustrated at all positions apart from position 7 which is non-degenerate by the stacked letters at each position. The relative height of each letter is proportional to its over-enrichment in the motif. A dashed line is boxed around <i>rs2205960-T</i>, this SLE-associated allele is predicted to form the 8<sup>th</sup> nucleotide in the motif. Predictions were made using the non-degenerate set of matrix profiles in the Jaspar Core database. <i>B</i>. Altering the <i>rs2205960</i> allele from <i>-T</i> to <i>-G</i> decreases the binding affinity for NF-κB p65 by over 10%. <i>C</i>. Binding of NF-κB at <i>rs2205960</i>, suggested by genome-wide ChIP-seq ENCODE data. Profiles were generated for lymphoblatoid cell lines and stored in the UCSC genome database.</p>", "links"=>[], "tags"=>["genetics", "Genetics of disease", "Human genetics", "Molecular genetics", "population genetics", "immunology", "Genetics of the immune system", "decameric", "motif", "p65"], "article_id"=>747884, "categories"=>["Biological Sciences"], "users"=>["Harinder Manku", "Carl D. Langefeld", "Sandra G. Guerra", "Talat H. Malik", "Marta Alarcon-Riquelme", "Juan-Manuel Anaya", "Sang-Cheol Bae", "Susan A. Boackle", "Elizabeth E. Brown", "Lindsey A. Criswell", "Barry I. Freedman", "Patrick M. Gaffney", "Peter A. Gregersen", "Joel M. Guthridge", "Sang-Hoon Han", "John B. Harley", "Chaim O. Jacob", "Judith A. James", "Diane L. Kamen", "Kenneth M. Kaufman", "Jennifer A. Kelly", "Javier Martin", "Joan T. Merrill", "Kathy L. Moser", "Timothy B. Niewold", "So-Yeon Park", "Bernardo A. Pons-Estel", "Amr H. Sawalha", "R. Hal Scofield", "Nan Shen", "Anne M. Stevens", "Celi Sun", "Gary S. Gilkeson", "Jeff C. Edberg", "Robert P. Kimberly", "Swapan K. Nath", "Betty P. Tsao", "Tim J. Vyse"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1003554.g006", "stats"=>{"downloads"=>3, "page_views"=>140, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_SLE_associated_rs2205960_predicted_to_be_part_of_a_decameric_motif_for_NF_B_p65_RELA_/747884", "title"=>"SLE-associated <i>rs2205960</i> predicted to be part of a decameric motif for NF-κB p65 (RELA).", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-07-18 02:09:50"}
  • {"files"=>["https://ndownloader.figshare.com/files/1121894"], "description"=>"<p>Numbers after filtering for duplicates, FDRs, HWE, missingness and major ancestry. post SNPs with INFO scores <0.7 excluded, SNPS with HWE<0.01 excluded.</p>", "links"=>[], "tags"=>["genetics", "Genetics of disease", "Human genetics", "Molecular genetics", "population genetics", "immunology", "Genetics of the immune system", "demographics", "imputation", "sle-control", "cohorts", "qc"], "article_id"=>747886, "categories"=>["Biological Sciences"], "users"=>["Harinder Manku", "Carl D. Langefeld", "Sandra G. Guerra", "Talat H. Malik", "Marta Alarcon-Riquelme", "Juan-Manuel Anaya", "Sang-Cheol Bae", "Susan A. Boackle", "Elizabeth E. Brown", "Lindsey A. Criswell", "Barry I. Freedman", "Patrick M. Gaffney", "Peter A. Gregersen", "Joel M. Guthridge", "Sang-Hoon Han", "John B. Harley", "Chaim O. Jacob", "Judith A. James", "Diane L. Kamen", "Kenneth M. Kaufman", "Jennifer A. Kelly", "Javier Martin", "Joan T. Merrill", "Kathy L. Moser", "Timothy B. Niewold", "So-Yeon Park", "Bernardo A. Pons-Estel", "Amr H. Sawalha", "R. Hal Scofield", "Nan Shen", "Anne M. Stevens", "Celi Sun", "Gary S. Gilkeson", "Jeff C. Edberg", "Robert P. Kimberly", "Swapan K. Nath", "Betty P. Tsao", "Tim J. Vyse"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1003554.t001", "stats"=>{"downloads"=>1, "page_views"=>12, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Population_demographics_and_imputation_reference_data_for_SLE_control_cohorts_post_QC_filtering_/747886", "title"=>"Population demographics and imputation reference data for SLE-control cohorts post QC filtering.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-07-18 02:09:50"}
  • {"files"=>["https://ndownloader.figshare.com/files/1121895"], "description"=>"<p>Variants in bold are imputed using 1000 Genomes phase 1 (v3).</p>", "links"=>[], "tags"=>["genetics", "Genetics of disease", "Human genetics", "Molecular genetics", "population genetics", "immunology", "Genetics of the immune system", "asian", "european", "hispanic", "sle-control"], "article_id"=>747887, "categories"=>["Biological Sciences"], "users"=>["Harinder Manku", "Carl D. Langefeld", "Sandra G. Guerra", "Talat H. Malik", "Marta Alarcon-Riquelme", "Juan-Manuel Anaya", "Sang-Cheol Bae", "Susan A. Boackle", "Elizabeth E. Brown", "Lindsey A. Criswell", "Barry I. Freedman", "Patrick M. Gaffney", "Peter A. Gregersen", "Joel M. Guthridge", "Sang-Hoon Han", "John B. Harley", "Chaim O. Jacob", "Judith A. James", "Diane L. Kamen", "Kenneth M. Kaufman", "Jennifer A. Kelly", "Javier Martin", "Joan T. Merrill", "Kathy L. Moser", "Timothy B. Niewold", "So-Yeon Park", "Bernardo A. Pons-Estel", "Amr H. Sawalha", "R. Hal Scofield", "Nan Shen", "Anne M. Stevens", "Celi Sun", "Gary S. Gilkeson", "Jeff C. Edberg", "Robert P. Kimberly", "Swapan K. Nath", "Betty P. Tsao", "Tim J. Vyse"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1003554.t002", "stats"=>{"downloads"=>1, "page_views"=>14, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Single_marker_association_results_for_East_Asian_As_European_Eur_and_Hispanic_Hisp_SLE_control_cohorts_/747887", "title"=>"Single marker association results for East Asian (As), European (Eur) and Hispanic (Hisp) SLE-control cohorts.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-07-18 02:09:50"}
  • {"files"=>["https://ndownloader.figshare.com/files/1121896"], "description"=>"<p>The first three columns list SNP characteristics, the next six columns list meta-analysis results including allele frequencies (FREQ1) and two-tailed P value for the nominal SNP association, conditioned on rs2205960, rs1234314 or conditioned on both rs1234314+rs2205960.</p>", "links"=>[], "tags"=>["genetics", "Genetics of disease", "Human genetics", "Molecular genetics", "population genetics", "immunology", "Genetics of the immune system", "meta-analysis"], "article_id"=>747888, "categories"=>["Biological Sciences"], "users"=>["Harinder Manku", "Carl D. Langefeld", "Sandra G. Guerra", "Talat H. Malik", "Marta Alarcon-Riquelme", "Juan-Manuel Anaya", "Sang-Cheol Bae", "Susan A. Boackle", "Elizabeth E. Brown", "Lindsey A. Criswell", "Barry I. Freedman", "Patrick M. Gaffney", "Peter A. Gregersen", "Joel M. Guthridge", "Sang-Hoon Han", "John B. Harley", "Chaim O. Jacob", "Judith A. James", "Diane L. Kamen", "Kenneth M. Kaufman", "Jennifer A. Kelly", "Javier Martin", "Joan T. Merrill", "Kathy L. Moser", "Timothy B. Niewold", "So-Yeon Park", "Bernardo A. Pons-Estel", "Amr H. Sawalha", "R. Hal Scofield", "Nan Shen", "Anne M. Stevens", "Celi Sun", "Gary S. Gilkeson", "Jeff C. Edberg", "Robert P. Kimberly", "Swapan K. Nath", "Betty P. Tsao", "Tim J. Vyse"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1003554.t003", "stats"=>{"downloads"=>1, "page_views"=>12, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Best_evidence_meta_analysis_of_the_association_P_value_for_TNFSF4_SNPs_/747888", "title"=>"Best evidence meta-analysis of the association P value for <i>TNFSF4</i> SNPs.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-07-18 02:09:50"}
  • {"files"=>["https://ndownloader.figshare.com/files/1121897"], "description"=>"<p>Conditional analyses in SNPTESTv2 Case Control. Continuous covariate within a clustering framework. P values selected using additional model and a frequentist paradigm.</p>", "links"=>[], "tags"=>["genetics", "Genetics of disease", "Human genetics", "Molecular genetics", "population genetics", "immunology", "Genetics of the immune system", "regression", "variants"], "article_id"=>747889, "categories"=>["Biological Sciences"], "users"=>["Harinder Manku", "Carl D. Langefeld", "Sandra G. Guerra", "Talat H. Malik", "Marta Alarcon-Riquelme", "Juan-Manuel Anaya", "Sang-Cheol Bae", "Susan A. Boackle", "Elizabeth E. Brown", "Lindsey A. Criswell", "Barry I. Freedman", "Patrick M. Gaffney", "Peter A. Gregersen", "Joel M. Guthridge", "Sang-Hoon Han", "John B. Harley", "Chaim O. Jacob", "Judith A. James", "Diane L. Kamen", "Kenneth M. Kaufman", "Jennifer A. Kelly", "Javier Martin", "Joan T. Merrill", "Kathy L. Moser", "Timothy B. Niewold", "So-Yeon Park", "Bernardo A. Pons-Estel", "Amr H. Sawalha", "R. Hal Scofield", "Nan Shen", "Anne M. Stevens", "Celi Sun", "Gary S. Gilkeson", "Jeff C. Edberg", "Robert P. Kimberly", "Swapan K. Nath", "Betty P. Tsao", "Tim J. Vyse"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1003554.t004", "stats"=>{"downloads"=>1, "page_views"=>12, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Conditional_regression_results_for_5_8242_TNFSF4_variants_in_four_groups_/747889", "title"=>"Conditional regression results for 5′TNFSF4 variants in four groups.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-07-18 02:09:50"}
  • {"files"=>["https://ndownloader.figshare.com/files/1121898"], "description"=>"<p><i>TNFSF4</i> haplotype association in four SLE-control populations.</p>", "links"=>[], "tags"=>["genetics", "Genetics of disease", "Human genetics", "Molecular genetics", "population genetics", "immunology", "Genetics of the immune system", "haplotype", "sle-control"], "article_id"=>747890, "categories"=>["Biological Sciences"], "users"=>["Harinder Manku", "Carl D. Langefeld", "Sandra G. Guerra", "Talat H. Malik", "Marta Alarcon-Riquelme", "Juan-Manuel Anaya", "Sang-Cheol Bae", "Susan A. Boackle", "Elizabeth E. Brown", "Lindsey A. Criswell", "Barry I. Freedman", "Patrick M. Gaffney", "Peter A. Gregersen", "Joel M. Guthridge", "Sang-Hoon Han", "John B. Harley", "Chaim O. Jacob", "Judith A. James", "Diane L. Kamen", "Kenneth M. Kaufman", "Jennifer A. Kelly", "Javier Martin", "Joan T. Merrill", "Kathy L. Moser", "Timothy B. Niewold", "So-Yeon Park", "Bernardo A. Pons-Estel", "Amr H. Sawalha", "R. Hal Scofield", "Nan Shen", "Anne M. Stevens", "Celi Sun", "Gary S. Gilkeson", "Jeff C. Edberg", "Robert P. Kimberly", "Swapan K. Nath", "Betty P. Tsao", "Tim J. Vyse"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1003554.t005", "stats"=>{"downloads"=>1, "page_views"=>16, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_TNFSF4_haplotype_association_in_four_SLE_control_populations_/747890", "title"=>"<i>TNFSF4</i> haplotype association in four SLE-control populations.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-07-18 02:09:50"}
  • {"files"=>["https://ndownloader.figshare.com/files/1121908", "https://ndownloader.figshare.com/files/1121909", "https://ndownloader.figshare.com/files/1121910", "https://ndownloader.figshare.com/files/1121911", "https://ndownloader.figshare.com/files/1121912", "https://ndownloader.figshare.com/files/1121913"], "description"=>"<div><p>We previously established an 80 kb haplotype upstream of <i>TNFSF4</i> as a susceptibility locus in the autoimmune disease SLE. SLE-associated alleles at this locus are associated with inflammatory disorders, including atherosclerosis and ischaemic stroke. In Europeans, the <i>TNFSF4</i> causal variants have remained elusive due to strong linkage disequilibrium exhibited by alleles spanning the region. Using a trans-ancestral approach to fine-map the locus, utilising 17,900 SLE and control subjects including Amerindian/Hispanics (1348 cases, 717 controls), African-Americans (AA) (1529, 2048) and better powered cohorts of Europeans and East Asians, we find strong association of risk alleles in all ethnicities; the AA association replicates in African-American Gullah (152,122). The best evidence of association comes from two adjacent markers: <i>rs2205960-T</i> (<i>P = 1.71×10<sup>−34</sup></i>, <i>OR = 1.43[1.26–1.60]</i>) and <i>rs1234317-T</i> (<i>P = 1.16×10<sup>−28</sup></i>, <i>OR = 1.38[1.24–1.54]</i>). Inference of fine-scale recombination rates for all populations tested finds the 80 kb risk and non-risk haplotypes in all except African-Americans. In this population the decay of recombination equates to an 11 kb risk haplotype, anchored in the 5′ region proximal to <i>TNFSF4</i> and tagged by <i>rs2205960-T</i> after 1000 Genomes phase 1 (v3) imputation. Conditional regression analyses delineate the 5′ risk signal to <i>rs2205960-T</i> and the independent non-risk signal to <i>rs1234314-C</i>. Our case-only and SLE-control cohorts demonstrate robust association of <i>rs2205960-T</i> with autoantibody production. The <i>rs2205960-T</i> is predicted to form part of a decameric motif which binds NF-κBp65 with increased affinity compared to <i>rs2205960-G</i>. ChIP-seq data also indicate NF-κB interaction with the DNA sequence at this position in LCL cells. Our research suggests association of <i>rs2205960-T</i> with SLE across multiple groups and an independent non-risk signal at <i>rs1234314-C</i>. <i>rs2205960-T</i> is associated with autoantibody production and lymphopenia. Our data confirm a global signal at <i>TNFSF4</i> and a role for the expressed product at multiple stages of lymphocyte dysregulation during SLE pathogenesis. We confirm the validity of trans-ancestral mapping in a complex trait.</p></div>", "links"=>[], "tags"=>["genetics", "Genetics of disease", "Human genetics", "Molecular genetics", "population genetics", "immunology", "Genetics of the immune system", "trans-ancestral", "studies", "sle-susceptibility", "locus"], "article_id"=>747899, "categories"=>["Biological Sciences"], "users"=>["Harinder Manku", "Carl D. Langefeld", "Sandra G. Guerra", "Talat H. Malik", "Marta Alarcon-Riquelme", "Juan-Manuel Anaya", "Sang-Cheol Bae", "Susan A. Boackle", "Elizabeth E. Brown", "Lindsey A. Criswell", "Barry I. Freedman", "Patrick M. Gaffney", "Peter A. Gregersen", "Joel M. Guthridge", "Sang-Hoon Han", "John B. Harley", "Chaim O. Jacob", "Judith A. James", "Diane L. Kamen", "Kenneth M. Kaufman", "Jennifer A. Kelly", "Javier Martin", "Joan T. Merrill", "Kathy L. Moser", "Timothy B. Niewold", "So-Yeon Park", "Bernardo A. Pons-Estel", "Amr H. Sawalha", "R. Hal Scofield", "Nan Shen", "Anne M. Stevens", "Celi Sun", "Gary S. Gilkeson", "Jeff C. Edberg", "Robert P. Kimberly", "Swapan K. Nath", "Betty P. Tsao", "Tim J. Vyse"], "doi"=>["https://dx.doi.org/10.1371/journal.pgen.1003554.s001", "https://dx.doi.org/10.1371/journal.pgen.1003554.s002", "https://dx.doi.org/10.1371/journal.pgen.1003554.s003", "https://dx.doi.org/10.1371/journal.pgen.1003554.s004", "https://dx.doi.org/10.1371/journal.pgen.1003554.s005", "https://dx.doi.org/10.1371/journal.pgen.1003554.s006"], "stats"=>{"downloads"=>50, "page_views"=>30, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Trans_Ancestral_Studies_Fine_Map_the_SLE_Susceptibility_Locus_TNFSF4_/747899", "title"=>"Trans-Ancestral Studies Fine Map the SLE-Susceptibility Locus <i>TNFSF4</i>", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2013-07-18 02:09:50"}
  • {"files"=>["https://ndownloader.figshare.com/files/1121875"], "description"=>"<p>1568 randomly assigned chromosomes from each group were tested using <i>Rhomap</i>, from the LDHAT2.0 package. The fine-scale map of recombination rate (4Ner/kb) was inferred across 200 kb of chromosome 1q25 encompassing <i>TNFSF4</i> gene and extended 5′ and 3′ regions.</p>", "links"=>[], "tags"=>["genetics", "Genetics of disease", "Human genetics", "Molecular genetics", "population genetics", "immunology", "Genetics of the immune system", "maps", "recombination", "inferred", "hispanic", "african-american", "phased"], "article_id"=>747868, "categories"=>["Biological Sciences"], "users"=>["Harinder Manku", "Carl D. Langefeld", "Sandra G. Guerra", "Talat H. Malik", "Marta Alarcon-Riquelme", "Juan-Manuel Anaya", "Sang-Cheol Bae", "Susan A. Boackle", "Elizabeth E. Brown", "Lindsey A. Criswell", "Barry I. Freedman", "Patrick M. Gaffney", "Peter A. Gregersen", "Joel M. Guthridge", "Sang-Hoon Han", "John B. Harley", "Chaim O. Jacob", "Judith A. James", "Diane L. Kamen", "Kenneth M. Kaufman", "Jennifer A. Kelly", "Javier Martin", "Joan T. Merrill", "Kathy L. Moser", "Timothy B. Niewold", "So-Yeon Park", "Bernardo A. Pons-Estel", "Amr H. Sawalha", "R. Hal Scofield", "Nan Shen", "Anne M. Stevens", "Celi Sun", "Gary S. Gilkeson", "Jeff C. Edberg", "Robert P. Kimberly", "Swapan K. Nath", "Betty P. Tsao", "Tim J. Vyse"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1003554.g001", "stats"=>{"downloads"=>0, "page_views"=>23, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Fine_scale_maps_of_recombination_rate_inferred_from_East_Asian_European_Hispanic_and_African_American_control_phased_chromosomes_/747868", "title"=>"Fine scale maps of recombination rate inferred from East Asian, European, Hispanic and African-American control phased chromosomes.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-07-18 02:09:50"}

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Relative Metric

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