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Only data requests in line with the Terms of Use will be taken into consideration. In addition to a completed request form, the Data Sharing Agreement (DSA) in line with GDPR regulations and/or the Research Collaboration Agreement (RCA) should be signed before data is shared. If a data request is approved, the data will be delivered in a safe and secure manner. By signing the DSA and/or RCA and accessing the Materials, the recipient represents his/her acceptance of the Terms of Use.  ","availabilityStatus":"The data is not available for download directly via DataverseNL but is available on request if the request is compliant with the Terms of Access. ","contactForAccess":"Please fill out the <a href=\"https://www.umcutrecht.nl/en/data-request-form-umc-utrecht\">request form</a>.","fileAccessRequest":true,"metadataBlocks":{"citation":{"displayName":"Citation Metadata","name":"citation","fields":[{"typeName":"title","multiple":false,"typeClass":"primitive","value":"A cis-regulatory element regulates ERAP2 expression through autoimmune disease risk SNPs"},{"typeName":"author","multiple":true,"typeClass":"compound","value":[{"authorName":{"typeName":"authorName","multiple":false,"typeClass":"primitive","value":"Jonas Kuiper"},"authorAffiliation":{"typeName":"authorAffiliation","multiple":false,"typeClass":"primitive","value":"UMC Utrecht"},"authorIdentifierScheme":{"typeName":"authorIdentifierScheme","multiple":false,"typeClass":"controlledVocabulary","value":"ORCID"},"authorIdentifier":{"typeName":"authorIdentifier","multiple":false,"typeClass":"primitive","value":"0000-0002-5370-6395"}}]},{"typeName":"datasetContact","multiple":true,"typeClass":"compound","value":[{"datasetContactName":{"typeName":"datasetContactName","multiple":false,"typeClass":"primitive","value":"data management"},"datasetContactAffiliation":{"typeName":"datasetContactAffiliation","multiple":false,"typeClass":"primitive","value":"UMC Utrecht"}},{"datasetContactName":{"typeName":"datasetContactName","multiple":false,"typeClass":"primitive","value":"Jonas Kuiper"},"datasetContactAffiliation":{"typeName":"datasetContactAffiliation","multiple":false,"typeClass":"primitive","value":"UMC Utrecht"}}]},{"typeName":"dsDescription","multiple":true,"typeClass":"compound","value":[{"dsDescriptionValue":{"typeName":"dsDescriptionValue","multiple":false,"typeClass":"primitive","value":"This dataset contains the summary statistics from regional association plots from GWAS, and conditional eQTL and pQTL analysis in GTEx data, and functional data as described in <i>Venema et al. 2023 \"A cis-regulatory element regulates ERAP2 expression through autoimmune disease risk SNPs </i> <dl>see preprint on <a href=\"https://www.biorxiv.org/content/10.1101/2023.03.03.530973v1\"><i>BioRxiv</i></a>\n</dl>\n\nThis dataverseNL dataset contains additional raw, processed, and metadata (see <a href=\"https://dataverse.nl/api/access/datafile/382543\">readme</a> file and reproducible R notebooks (R script and Image) used for the analysis in the manuscript: <br></br>\n<dl>\n<dt>R scripts (markdown + R image) with <i>step-by-step</i> analyses </dt> \n<ul>\n<li><dd>Figure_2.rmd (see <a href=\"https://dataverse.nl/api/access/datafile/382486\n\">\"Figure_2.html\"</a>)</dd></li>\n<li><dd>Figure_3.rmd (see <a href=\"https://dataverse.nl/api/access/datafile/382504\">\"Figure_3.html\"</a>)</dd>\n</li>\n<li><dd>Figure_4.rmd (see <a href=\"https://dataverse.nl/api/access/datafile/382462\">\"Figure_4.html\"</a>)</dd>\n</li>\n<li><dd>Cell line authentification (including COSMIC reference genotypes) (see folder <b>Appendix</b> in files)</dd></li></ul>\n\n<dt>Experimental data</dt>\n<ul><li><dd>The qPCR (Ct value) data for each experiment are outlined the Supplemental Tables (see <a href=\"https://dataverse.nl/api/access/datafile/382478\">here</a>)</dd></li>\n<li><dd>The 4C seq data (FASTA and wig files) for the 3 birdshot LCLs can be found in subdirectory of Figure 4 </dd></li>\n<li><dd>Copy-number SNP-array data for CRISPR-edited cell lines (see folder \"SNP_array_Data\" and an example of THP-1 can be found <a href=\"https://dataverse.nl/api/access/datafile/382483\">here</a>)</dd></li></ul>\n\n<dt>Other data used in the manuscript and R scripts</dt> \n\n<ul><li><dd><a href=\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9725108/bin/NIHMS1809843-supplement-TableS4.txt\">MPRA of ERAP2 eQTLs</i> </a> as reported by <a href=\"https://pubmed.ncbi.nlm.nih.gov/35298243/\"><i> Abell et al. Science 2022</i> </a></li>\n\n<li><dd><a href=\"https://static-content.springer.com/esm/art%3A10.1038%2Fs41588-020-00745-3/MediaObjects/41588_2020_745_MOESM3_ESM.xlsx\">H3K27ac Chip combined with HiC</i> </a> in primary immune cell subsets generated by <a href=\"https://pubmed.ncbi.nlm.nih.gov/33349701/\"><i> Chandra et al., Nat Genet. 2021</i> </a></li>\n\n<li><dd>Supplemental <a href=\"https://dataverse.nl/api/access/datafile/382484\">data</i> </a> originally generated and provided upon request by <a href=\"https://pubmed.ncbi.nlm.nih.gov/36819665/\"><i> Kerner et al., Cell Genomics 2023</i> </a></li>\n\n<li><dd>Summary statistics of ERAP2 eQTL analysis in <a href=\"https://console.cloud.google.com/storage/browser/gtex-resources\">whole blood</i> </a> generated by <a href=\"https://www.science.org/doi/10.1126/science.aaz1776\"><i> GTEx Consortium </i> </a></li>\n\n<li><dd>Summary statistics of ERAP2 pQTL analysis in <a href=\"https://app.box.com/s/u3flbp13zjydegrxjb2uepagp1vb6bj2\">human plasma</i> </a> generated in the INTERVAL study by <a href=\"https://pubmed.ncbi.nlm.nih.gov/29875488/\"><i> Sun et al Nature 2018 </i> </a></li>\n\n<li><dd>Summary statistics of <i>5q15</i> of GWAS in <a href=\"https://dataverse.nl/api/access/datafile/382440\">Birdshot chorioretinopathy</i> </a> (full GWAS summary stats [>1GB] are available in folder \"Figure 2/GWAS_summary_stats\") generated by <a href=\"https://pubmed.ncbi.nlm.nih.gov/24957906/\"><i> Kuiper et al Hum Mol Gen 2014</i> </a></li>\n\n<li><dd>Summary statistics of GWAS in <a href=\"https://www.ibdgenetics.org/uploads/cd-meta.txt.gz\">Crohn's Disease</i> </a> generated by <a href=\"https://www.nature.com/articles/ng.717\"><i> Franke et al Nat Genet 2010 </i> </a></li>\n\n<li><dd>Summary statistics of <i>5q15</i> of GWAS in <a href=\"https://dataverse.nl/api/access/datafile/382488\">JIA</i> </a> generated by <a href=\"https://pubmed.ncbi.nlm.nih.gov/23603761/\"><i> Hinks et al Nat Genet 2013 </i> </a></li>\n\n</dl>"},"dsDescriptionDate":{"typeName":"dsDescriptionDate","multiple":false,"typeClass":"primitive","value":"2023-10-2"}}]},{"typeName":"subject","multiple":true,"typeClass":"controlledVocabulary","value":["Medicine, Health and Life Sciences"]},{"typeName":"publication","multiple":true,"typeClass":"compound","value":[{"publicationCitation":{"typeName":"publicationCitation","multiple":false,"typeClass":"primitive","value":"https://www.biorxiv.org/content/10.1101/2023.03.03.530973v1"},"publicationURL":{"typeName":"publicationURL","multiple":false,"typeClass":"primitive","value":"https://www.biorxiv.org/content/10.1101/2023.03.03.530973v1"}}]},{"typeName":"notesText","multiple":false,"typeClass":"primitive","value":"Single nucleotide polymorphisms (SNP) near the ERAP2 gene are associated with autoimmune conditions such as Crohn’s disease, and birdshot chorioretinopathy, as well as protection against lethal infections, including the Black Death. Due to high linkage disequilibrium (LD), a great number of trait-associated SNPs are correlated with ERAP2 expression, however their functional mechanisms remain unidentified. We used genome editing and functional genomics to identify causal variants that remain obscured by LD. We demonstrate by reciprocal allelic replacement that ERAP2 expression is directly controlled by the genotype of splice region SNP rs2248374. However, we demonstrate that autoimmune disease-risk SNPs located near the downstream LNPEP gene promoter are independently associated with ERAP2 expression. Allele-specific conformation capture assays revealed long-range chromatin contacts between the LNPEP promoter region and the ERAP2 promoter and showed that interactions were stronger in patients carrying the alleles that increase susceptibility to autoimmune diseases. Replacing the disease-associated SNPs in the LNPEP promoter by reference sequences lowered ERAP2 expression. These findings show that clustered GWAS signals associated with diverse autoimmune conditions and lethal infections act in concert to control ERAP2 expression and that disease-associated variants can convert a gene promoter region into a potent enhancer of a distal gene."},{"typeName":"productionDate","multiple":false,"typeClass":"primitive","value":"2023-10-02"},{"typeName":"productionPlace","multiple":true,"typeClass":"primitive","value":["University Medical Center Utrecht, The Netherlands"]},{"typeName":"grantNumber","multiple":true,"typeClass":"compound","value":[{"grantNumberAgency":{"typeName":"grantNumberAgency","multiple":false,"typeClass":"primitive","value":"Stichting Lijf en Leven"},"grantNumberValue":{"typeName":"grantNumberValue","multiple":false,"typeClass":"primitive","value":"63"}},{"grantNumberAgency":{"typeName":"grantNumberAgency","multiple":false,"typeClass":"primitive","value":"Uitzicht"},"grantNumberValue":{"typeName":"grantNumberValue","multiple":false,"typeClass":"primitive","value":"2018-1"}}]},{"typeName":"depositor","multiple":false,"typeClass":"primitive","value":"Kuiper, Jonas"},{"typeName":"dateOfDeposit","multiple":false,"typeClass":"primitive","value":"2023-10-03"},{"typeName":"relatedDatasets","multiple":true,"typeClass":"primitive","value":["See description of the data for related datasets"]}]},"dansDataVaultMetadata":{"displayName":"Data Vault 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