{"doi":"10.1101/2020.01.20.906701","title":"Genome-wide discovery of SLE genetic risk variant allelic enhancer activity","abstract":"Abstract Genome-wide association studies of Systemic Lupus Erythematosus (SLE) nominate 3,073 genetic variants at 91 risk loci. To systematically screen these variants for allelic transcriptional enhancer activity, we constructed a massively parallel reporter assay (MPRA) library comprising 12,396 DNA oligonucleotides containing the genomic context around every allele of each SLE variant. Transfection into the Epstein-Barr virus-transformed B cell line GM12878 revealed 482 variants with enhancer activity, with 51 variants showing genotype-dependent (allelic) enhancer activity at 27 risk loci. Comparison of MPRA results in GM12878 and Jurkat T cell lines highlights shared and unique allelic transcriptional regulatory mechanisms at SLE risk loci. In-depth analysis of allelic transcription factor (TF) binding at and around allelic variants identifies one class of TFs whose DNA-binding motif tends to be directly altered by the risk variant and a second, larger class of TFs that bind allelically without direct alteration of their motif by the variant. Collectively, our approach provides a blueprint for the discovery of allelic gene regulation at risk loci for any disease and offers insight into the transcriptional regulatory mechanisms underlying SLE.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":122529,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.8114,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":229081,"name":"Xiaoting Chen","orcid":"0000-0002-3782-3962","position":1,"is_corresponding":false},{"id":564211,"name":"Carmy Forney","orcid":null,"position":2,"is_corresponding":false},{"id":564212,"name":"Omer Donmez","orcid":null,"position":3,"is_corresponding":false},{"id":564213,"name":"Daniel Miller","orcid":null,"position":4,"is_corresponding":false},{"id":250977,"name":"Sreeja Parameswaran","orcid":"0009-0002-3631-3669","position":5,"is_corresponding":false},{"id":290645,"name":"Ted Hong","orcid":null,"position":6,"is_corresponding":false},{"id":110127,"name":"Yongbo Huang","orcid":"0000-0001-6798-0451","position":7,"is_corresponding":false},{"id":301665,"name":"Mario Pujato","orcid":"0000-0002-2415-3111","position":8,"is_corresponding":false},{"id":564214,"name":"Tareian Cazares","orcid":null,"position":9,"is_corresponding":false},{"id":90196,"name":"Emily R. Miraldi","orcid":"0000-0002-0232-3116","position":10,"is_corresponding":false},{"id":3028,"name":"John P. Ray","orcid":null,"position":11,"is_corresponding":false},{"id":3029,"name":"Carl G. de Boer","orcid":"0000-0001-8935-5921","position":12,"is_corresponding":false},{"id":343978,"name":"John B. Harley","orcid":"0000-0002-8463-1939","position":13,"is_corresponding":false},{"id":19923,"name":"Matthew T. Weirauch","orcid":"0000-0001-7977-9122","position":14,"is_corresponding":false},{"id":250976,"name":"Leah C. Kottyan","orcid":"0000-0003-3979-2220","position":15,"is_corresponding":false},{"id":564210,"name":"Xiaoming Lu","orcid":null,"position":0,"is_corresponding":true}],"reference_count":122,"raw_metadata":null,"created_at":"2026-07-18T23:14:51.076430Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}