Genome-Wide Association Study of African and European Americans Implicates Multiple Shared and Ethnic Specific Loci in Sarcoidosis Susceptibility
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{"title"=>"Genome-wide association study of African and European Americans implicates multiple shared and ethnic specific loci in sarcoidosis susceptibility", "type"=>"journal", "authors"=>[{"first_name"=>"Indra", "last_name"=>"Adrianto", "scopus_author_id"=>"15022036800"}, {"first_name"=>"Chee Paul", "last_name"=>"Lin", "scopus_author_id"=>"36463818100"}, {"first_name"=>"Jessica J.", "last_name"=>"Hale", "scopus_author_id"=>"55344277900"}, {"first_name"=>"Albert M.", "last_name"=>"Levin", "scopus_author_id"=>"7403194355"}, {"first_name"=>"Indrani", "last_name"=>"Datta", "scopus_author_id"=>"57186410700"}, {"first_name"=>"Ryan", "last_name"=>"Parker", "scopus_author_id"=>"55344704700"}, {"first_name"=>"Adam", "last_name"=>"Adler", "scopus_author_id"=>"57197122251"}, {"first_name"=>"Jennifer A.", "last_name"=>"Kelly", "scopus_author_id"=>"8536891600"}, {"first_name"=>"Kenneth M.", "last_name"=>"Kaufman", "scopus_author_id"=>"7102773191"}, {"first_name"=>"Christopher J.", "last_name"=>"Lessard", "scopus_author_id"=>"24481494000"}, {"first_name"=>"Kathy L.", "last_name"=>"Moser", "scopus_author_id"=>"7202172981"}, {"first_name"=>"Robert P.", "last_name"=>"Kimberly", "scopus_author_id"=>"7005738540"}, {"first_name"=>"John B.", "last_name"=>"Harley", "scopus_author_id"=>"7201902945"}, {"first_name"=>"Michael C.", "last_name"=>"Iannuzzi", "scopus_author_id"=>"7006338485"}, {"first_name"=>"Benjamin A.", "last_name"=>"Rybicki", "scopus_author_id"=>"7006410465"}, {"first_name"=>"Courtney G.", "last_name"=>"Montgomery", "scopus_author_id"=>"36898775500"}], "year"=>2012, "source"=>"PLoS ONE", "identifiers"=>{"scopus"=>"2-s2.0-84865443261", "sgr"=>"84865443261", "doi"=>"10.1371/journal.pone.0043907", "pui"=>"365513967", "pmid"=>"22952805", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)", "issn"=>"19326203"}, "id"=>"33758292-2dc5-3f42-b5d9-990d16b0fa67", "abstract"=>"Sarcoidosis is a systemic inflammatory disease characterized by the formation of granulomas in affected organs. Genome-wide association studies (GWASs) of this disease have been conducted only in European population. We present the first sarcoidosis GWAS in African Americans (AAs, 818 cases and 1,088 related controls) followed by replication in independent sets of AAs (455 cases and 557 controls) and European Americans (EAs, 442 cases and 2,284 controls). We evaluated >6 million SNPs either genotyped using the Illumina Omni1-Quad array or imputed from the 1000 Genomes Project data. We identified a novel sarcoidosis-associated locus, NOTCH4, that reached genome-wide significance in the combined AA samples (rs715299, P(AA-meta) = 6.51 × 10(-10)) and demonstrated the independence of this locus from others in the MHC region in the same sample. We replicated previous European GWAS associations within HLA-DRA, HLA-DRB5, HLA-DRB1, BTNL2, and ANXA11 in both our AA and EA datasets. We also confirmed significant associations to the previously reported HLA-C and HLA-B regions in the EA but not AA samples. We further identified suggestive associations with several other genes previously reported in lung or inflammatory diseases.", "link"=>"http://www.mendeley.com/research/genomewide-association-study-african-european-americans-implicates-multiple-shared-ethnic-specific-l", "reader_count"=>28, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>3, "Librarian"=>1, "Researcher"=>9, "Student > Ph. D. Student"=>4, "Student > Master"=>3, "Other"=>2, "Student > Bachelor"=>2, "Professor"=>4}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>3, "Librarian"=>1, "Researcher"=>9, "Student > Ph. D. Student"=>4, "Student > Master"=>3, "Other"=>2, "Student > Bachelor"=>2, "Professor"=>4}, "reader_count_by_subject_area"=>{"Unspecified"=>2, "Engineering"=>1, "Environmental Science"=>1, "Biochemistry, Genetics and Molecular Biology"=>5, "Mathematics"=>1, "Agricultural and Biological Sciences"=>8, "Medicine and Dentistry"=>10}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>1}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>10}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>8}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>5}, "Mathematics"=>{"Mathematics"=>1}, "Unspecified"=>{"Unspecified"=>2}, "Environmental Science"=>{"Environmental Science"=>1}}, "reader_count_by_country"=>{"United States"=>3, "Spain"=>1}, "group_count"=>4}

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Figshare

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  • {"files"=>["https://ndownloader.figshare.com/files/586338"], "description"=>"<p>(A–D) Association results in the AA discovery set (A), a meta-analysis between the AA discovery and AA replication sets (B), the EA dataset (C), and a meta-analysis of the AA discovery, AA replication and EA datasets (D). The black horizontal line represents the threshold for genome-wide significance (<i>P</i><5×10<sup>−8</sup>) and the gray line is the suggestive evidence of association threshold (<i>P</i><1×10<sup>−4</sup>).</p>", "links"=>[], "tags"=>["plots", "snp-sarcoidosis"], "article_id"=>256808, "categories"=>["Biological Sciences", "Genetics", "Evolutionary Biology"], "users"=>["Indra Adrianto", "Chee Paul Lin", "Jessica J. Hale", "Albert M. Levin", "Indrani Datta", "Ryan Parker", "Adam Adler", "Jennifer A. Kelly", "Kenneth M. Kaufman", "Christopher J. Lessard", "Kathy L. Moser", "Robert P. Kimberly", "John B. Harley", "Michael C. Iannuzzi", "Benjamin A. Rybicki", "Courtney G. Montgomery"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0043907.g002", "stats"=>{"downloads"=>0, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Manhattan_plots_of_SNP_sarcoidosis_association_test_results_/256808", "title"=>"Manhattan plots of SNP-sarcoidosis association test results.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-08-27 01:53:28"}
  • {"files"=>["https://ndownloader.figshare.com/files/586519"], "description"=>"<p>(A–D) Association results in the AA discovery set (A), AA replication set (B), a meta-analysis between the AA discovery and AA replication sets (C), the EA dataset (D), and a meta-analysis of the AA discovery, AA replication and EA datasets (E). Each SNP is colored according to its LD (<i>r</i><sup>2</sup>) with the top SNP, except for (E) since the meta-analysis was performed on two different populations. The recombination rate is denoted by the blue solid line. Plots were drawn using LocusZoom <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0043907#pone.0043907-Pruim1\" target=\"_blank\">[100]</a>.</p>", "links"=>[], "tags"=>["plots", "snp-sarcoidosis", "mhc", "ii"], "article_id"=>256995, "categories"=>["Biological Sciences", "Genetics", "Evolutionary Biology"], "users"=>["Indra Adrianto", "Chee Paul Lin", "Jessica J. Hale", "Albert M. Levin", "Indrani Datta", "Ryan Parker", "Adam Adler", "Jennifer A. Kelly", "Kenneth M. Kaufman", "Christopher J. Lessard", "Kathy L. Moser", "Robert P. Kimberly", "John B. Harley", "Michael C. Iannuzzi", "Benjamin A. Rybicki", "Courtney G. Montgomery"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0043907.g003", "stats"=>{"downloads"=>0, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Regional_association_plots_of_SNP_sarcoidosis_association_test_results_within_the_MHC_Class_II_region_/256995", "title"=>"Regional association plots of SNP-sarcoidosis association test results within the MHC Class II region.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-08-27 01:56:35"}
  • {"files"=>["https://ndownloader.figshare.com/files/586792"], "description"=>"1<p>Major/minor allele of AAs as the reference;</p>2<p>Minor allele frequency;</p>3<p>The odds ratio (OR) was calculated with respect to the minor allele of AAs.</p>a<p>Previously reported sarcoidosis loci meeting genome-wide significance in the AA discovery set.</p>b<p>Potentially novel region meeting genome-wide significance after the meta-analysis of AA datasets.</p>c<p>Previously reported sarcoidosis loci meeting genome-wide significance in the EA dataset.</p><p>Note that stepwise conditional analysis results to identify independent signals within the MHC region can be found in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0043907#pone.0043907.s006\" target=\"_blank\">Tables S3</a> and <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0043907#pone.0043907.s007\" target=\"_blank\">S4</a>.</p>", "links"=>[], "tags"=>["genome-wide", "snps", "grouped"], "article_id"=>257268, "categories"=>["Biological Sciences", "Genetics", "Evolutionary Biology"], "users"=>["Indra Adrianto", "Chee Paul Lin", "Jessica J. Hale", "Albert M. Levin", "Indrani Datta", "Ryan Parker", "Adam Adler", "Jennifer A. Kelly", "Kenneth M. Kaufman", "Christopher J. Lessard", "Kathy L. Moser", "Robert P. Kimberly", "John B. Harley", "Michael C. Iannuzzi", "Benjamin A. Rybicki", "Courtney G. Montgomery"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0043907.t002", "stats"=>{"downloads"=>1, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Regions_of_association_meeting_genome_wide_significance_and_their_most_significant_SNPs_grouped_by_sample_/257268", "title"=>"Regions of association meeting genome-wide significance and their most significant SNPs grouped by sample.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2012-08-27 02:01:08"}
  • {"files"=>["https://ndownloader.figshare.com/files/308247", "https://ndownloader.figshare.com/files/308304", "https://ndownloader.figshare.com/files/308389", "https://ndownloader.figshare.com/files/308454", "https://ndownloader.figshare.com/files/308503", "https://ndownloader.figshare.com/files/308522", "https://ndownloader.figshare.com/files/308540", "https://ndownloader.figshare.com/files/308557", "https://ndownloader.figshare.com/files/308603"], "description"=>"<div><p>Sarcoidosis is a systemic inflammatory disease characterized by the formation of granulomas in affected organs. Genome-wide association studies (GWASs) of this disease have been conducted only in European population. We present the first sarcoidosis GWAS in African Americans (AAs, 818 cases and 1,088 related controls) followed by replication in independent sets of AAs (455 cases and 557 controls) and European Americans (EAs, 442 cases and 2,284 controls). We evaluated >6 million SNPs either genotyped using the Illumina Omni1-Quad array or imputed from the 1000 Genomes Project data. We identified a novel sarcoidosis-associated locus, <em>NOTCH4</em>, that reached genome-wide significance in the combined AA samples (rs715299, <em>P</em><sub>AA-meta</sub> = 6.51×10<sup>−10</sup>) and demonstrated the independence of this locus from others in the MHC region in the same sample. We replicated previous European GWAS associations within <em>HLA-DRA, HLA-DRB5, HLA-DRB1</em>, <em>BTNL2,</em> and <em>ANXA11</em> in both our AA and EA datasets. We also confirmed significant associations to the previously reported <em>HLA-C</em> and <em>HLA-B</em> regions in the EA but not AA samples. We further identified suggestive associations with several other genes previously reported in lung or inflammatory diseases.</p> </div>", "links"=>[], "tags"=>["genome-wide", "african", "european", "americans", "implicates", "loci", "sarcoidosis", "susceptibility"], "article_id"=>120816, "categories"=>["Biological Sciences", "Genetics", "Evolutionary Biology"], "users"=>["Indra Adrianto", "Chee Paul Lin", "Jessica J. Hale", "Albert M. Levin", "Indrani Datta", "Ryan Parker", "Adam Adler", "Jennifer A. Kelly", "Kenneth M. Kaufman", "Christopher J. Lessard", "Kathy L. Moser", "Robert P. Kimberly", "John B. Harley", "Michael C. Iannuzzi", "Benjamin A. Rybicki", "Courtney G. Montgomery"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0043907.s001", "https://dx.doi.org/10.1371/journal.pone.0043907.s002", "https://dx.doi.org/10.1371/journal.pone.0043907.s003", "https://dx.doi.org/10.1371/journal.pone.0043907.s004", "https://dx.doi.org/10.1371/journal.pone.0043907.s005", "https://dx.doi.org/10.1371/journal.pone.0043907.s006", "https://dx.doi.org/10.1371/journal.pone.0043907.s007", "https://dx.doi.org/10.1371/journal.pone.0043907.s008", "https://dx.doi.org/10.1371/journal.pone.0043907.s009"], "stats"=>{"downloads"=>5, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Genome_Wide_Association_Study_of_African_and_European_Americans_Implicates_Multiple_Shared_and_Ethnic_Specific_Loci_in_Sarcoidosis_Susceptibility/120816", "title"=>"Genome-Wide Association Study of African and European Americans Implicates Multiple Shared and Ethnic Specific Loci in Sarcoidosis Susceptibility", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2012-08-27 00:13:36"}
  • {"files"=>["https://ndownloader.figshare.com/files/586727"], "description"=>"1<p>Major/minor allele of AAs as the reference;</p>2<p>Minor allele frequency;</p>3<p>The odds ratio (OR) was calculated with respect to the minor allele of AAs.</p>", "links"=>[], "tags"=>["reported", "snps", "sarcoidosis"], "article_id"=>257206, "categories"=>["Biological Sciences", "Genetics", "Evolutionary Biology"], "users"=>["Indra Adrianto", "Chee Paul Lin", "Jessica J. Hale", "Albert M. Levin", "Indrani Datta", "Ryan Parker", "Adam Adler", "Jennifer A. Kelly", "Kenneth M. Kaufman", "Christopher J. Lessard", "Kathy L. Moser", "Robert P. Kimberly", "John B. Harley", "Michael C. Iannuzzi", "Benjamin A. Rybicki", "Courtney G. Montgomery"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0043907.t003", "stats"=>{"downloads"=>1, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Replication_of_previously_reported_SNPs_associated_with_sarcoidosis_9_11_25_27_/257206", "title"=>"Replication of previously reported SNPs associated with sarcoidosis [9], [11], [25], [27].", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2012-08-27 02:00:06"}
  • {"files"=>["https://ndownloader.figshare.com/files/586678"], "description"=>"a<p>Taken from the Illumina YRI-ASW iControlDB;</p>b<p>175 Caucasian healthy controls from the Illumina iControlDB, 1047 controls from the dbGaP GENEVA Melanoma study, and 1986 controls from the dbGAP CIDR: NGRC Parkinson’s Disease Study.</p>", "links"=>[], "tags"=>["genetics and genomics", "Computational biology", "Evolutionary biology"], "article_id"=>257153, "categories"=>["Biological Sciences", "Genetics", "Evolutionary Biology"], "users"=>["Indra Adrianto", "Chee Paul Lin", "Jessica J. Hale", "Albert M. Levin", "Indrani Datta", "Ryan Parker", "Adam Adler", "Jennifer A. Kelly", "Kenneth M. Kaufman", "Christopher J. Lessard", "Kathy L. Moser", "Robert P. Kimberly", "John B. Harley", "Michael C. Iannuzzi", "Benjamin A. Rybicki", "Courtney G. Montgomery"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0043907.t001", "stats"=>{"downloads"=>1, "page_views"=>12, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Sample_summary_before_and_after_quality_control_QC_/257153", "title"=>"Sample summary before and after quality control (QC).", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2012-08-27 01:59:13"}

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Relative Metric

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