{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T22:24:50Z","timestamp":1792448690472,"version":"4.5.0"},"reference-count":45,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2024,3,26]],"date-time":"2024-03-26T00:00:00Z","timestamp":1711411200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 AI172255"],"award-info":[{"award-number":["R01 AI172255"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R21 AI168943"],"award-info":[{"award-number":["R21 AI168943"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2024,7]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Systemic lupus erythematosus (SLE), an autoimmune disease with incompletely understood etiology, has a strong genetic component. Although genome\u2010wide association studies (GWASs) have revealed multiple SLE susceptibility loci and associated single\u2010nucleotide polymorphisms (SNPs), the precise causal variants, target genes, cell types, tissues, and mechanisms of action remain largely unknown.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Here, we report a comprehensive post\u2010GWAS analysis using extensive bioinformatics, molecular modeling, and integrative functional genomic and epigenomic analyses to optimize fine\u2010mapping. We compile and cross\u2010reference immune cell\u2013specific expression quantitative trait loci (cis\u2013 and trans\u2013expression quantitative trait loci) with promoter capture high\u2010throughput capture chromatin conformation (PCHi\u2010C), allele\u2010specific chromatin accessibility, and massively parallel reporter assay data to define predisposing variants and target genes. We experimentally validate a predicted locus using CRISPR\/Cas9 genome editing, quantitative polymerase chain reaction, and Western blot.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Anchoring on 452 index SNPs, we selected 9,931 high linkage disequilibrium (\n                      <jats:italic>r<\/jats:italic>\n                      <jats:sup>2<\/jats:sup>\n                      &gt; 0.8) SNPs and defined 182 independent non\u2010human leukocyte antigen (HLA) SLE loci. The 3,746 SNPs from 143 loci were identified as regulating 564 unique genes. Target genes are enriched in lupus\u2010related tissues and associated with other autoimmune diseases. Of these, 329 SNPs (106 loci) showed significant allele\u2010specific chromatin accessibility and\/or enhancer activity, indicating regulatory potential. Using CRISPR\/Cas9, we validated reference SNP identifier 57668933 (rs57668933) as a functional variant regulating multiple targets, including SLE\u2010risk gene\n                      <jats:italic>ELF1<\/jats:italic>\n                      in B cells.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>We demonstrate and validate post\u2010GWAS strategies for using multidimensional data to prioritize likely causal variants with cognate gene targets underlying SLE pathogenesis. Our results provide a catalog of significantly SLE\u2010associated SNPs and loci, target genes, and likely biochemical mechanisms to guide experimental characterization.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/art.42829","type":"journal-article","created":{"date-parts":[[2024,2,19]],"date-time":"2024-02-19T03:35:35Z","timestamp":1708313735000},"page":"1071-1084","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["A Multilayered Post\u2013\n                    <scp>Genome\u2010Wide<\/scp>\n                    Association Study Analysis Pipeline Defines Functional Variants and Target Genes for Systemic Lupus Erythematosus"],"prefix":"10.1002","volume":"76","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7979-758X","authenticated-orcid":false,"given":"Mehdi","family":"Fazel\u2010Najafabadi","sequence":"first","affiliation":[{"name":"Oklahoma Medical Research Foundation  Oklahoma City"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Loren L.","family":"Looger","sequence":"additional","affiliation":[{"name":"University of California  San Diego La Jolla"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harikrishna Reddy","family":"Rallabandi","sequence":"additional","affiliation":[{"name":"Oklahoma Medical Research Foundation  Oklahoma City"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6013-9328","authenticated-orcid":false,"given":"Swapan K.","family":"Nath","sequence":"additional","affiliation":[{"name":"Oklahoma Medical Research Foundation  Oklahoma City"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,3,26]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamainternmed.2015.3528"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780350310"},{"issue":"5","key":"e_1_2_6_4_1","first-page":"913","article-title":"A family survey of lupus erythematosus. 1. 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