{"doi":"10.1101/2024.07.15.24310442","title":"<i>Trans</i>\n                  -eQTL mapping prioritises\n                  <i>USP18</i>\n                  as a negative regulator of interferon response at a lupus risk locus","abstract":"<jats:title>Abstract</jats:title>\n                <jats:p>\n                  Although genome-wide association studies have provided valuable insights into the genetic basis of complex traits and diseases, translating these findings to causal genes and their downstream mechanisms remains challenging. We performed\n                  <jats:italic>trans</jats:italic>\n                  expression quantitative trait locus (\n                  <jats:italic>trans</jats:italic>\n                  -eQTL) meta-analysis in 3,734 lymphoblastoid cell line samples, identifying four robust loci that replicated in an independent multi-ethnic dataset of 682 individuals. We prioritised a missense variant in the ubiquitin specific peptidase 18 (\n                  <jats:italic>USP18)</jats:italic>\n                  gene that is a known negative regulator of interferon signalling and has previously been associated with increased risk of systemic lupus erythematosus (SLE). The SLE risk allele increased the expression of 50 interferon-inducible genes, suggesting that the risk allele impairs USP18’s ability to effectively limit the interferon response. Intriguingly, the\n                  <jats:italic>USP18 trans</jats:italic>\n                  -eQTL signal would not have been discovered in a meta-analysis of up to 43,301 whole blood samples, reaffirming the importance of capturing context-specific genetic effects for GWAS interpretation.\n                </jats:p>","journal":null,"year":null,"id":638802,"datarank":0.16479184330021646,"base_score":1.0986122886681096,"endowment":1.0986122886681096,"self_citation_contribution":0.16479184330021646,"citation_network_contribution":0.0,"self_endowment_contribution":0.16479184330021646,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":725428,"name":"Anneke Brümmer","orcid":"0000-0002-3576-0750","position":1,"is_corresponding":false},{"id":614309,"name":"Robert Warmerdam","orcid":"0000-0001-8691-0053","position":2,"is_corresponding":false},{"id":1659422,"name":"Tarran S. Rupall","orcid":"0009-0008-9274-7414","position":3,"is_corresponding":false},{"id":1582536,"name":"Ana Laura Hernández-Ledesma","orcid":"0000-0002-8819-7471","position":4,"is_corresponding":false},{"id":23921,"name":"Joshua Chiou","orcid":"0000-0002-4618-0647","position":5,"is_corresponding":false},{"id":612013,"name":"Emily Holzinger","orcid":"0000-0002-1298-4508","position":6,"is_corresponding":false},{"id":1659423,"name":"Joseph C. Maranville","orcid":null,"position":7,"is_corresponding":false},{"id":1659424,"name":"Nikolina Nakic","orcid":null,"position":8,"is_corresponding":false},{"id":329786,"name":"Halit Ongen","orcid":"0000-0002-4197-5790","position":9,"is_corresponding":false},{"id":614713,"name":"Luca Stefanucci","orcid":"0000-0002-4352-1151","position":10,"is_corresponding":false},{"id":571395,"name":"Michael C. Turchin","orcid":"0000-0003-3569-1529","position":11,"is_corresponding":false},{"id":108535,"name":"Lude Franke","orcid":"0000-0002-5159-8802","position":13,"is_corresponding":false},{"id":108546,"name":"Urmo Võsa","orcid":"0000-0003-3476-1652","position":14,"is_corresponding":false},{"id":1659425,"name":"Carla P. Jones","orcid":"0000-0002-4329-3267","position":15,"is_corresponding":false},{"id":713019,"name":"Alejandra Medina-Rivera","orcid":"0000-0002-7912-2718","position":16,"is_corresponding":false},{"id":43180,"name":"Gosia Trynka","orcid":"0000-0002-6955-9529","position":17,"is_corresponding":false},{"id":104224,"name":"Kai Kisand","orcid":"0000-0002-5426-4648","position":18,"is_corresponding":false},{"id":21856,"name":"Sven Bergmann","orcid":"0000-0002-6785-9034","position":19,"is_corresponding":false},{"id":550870,"name":"Kaur Alasoo","orcid":"0000-0002-1761-8881","position":20,"is_corresponding":false},{"id":1659421,"name":"Krista Freimann","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"<i>Trans</i>\n                  -eQTL mapping prioritises\n                  <i>USP18</i>\n                  as a negative regulator of interferon response at a lupus risk locus","abstract":"<jats:title>Abstract</jats:title>\n                <jats:p>\n                  Although genome-wide association studies have provided valuable insights into the genetic basis of complex traits and diseases, translating these findings to causal genes and their downstream mechanisms remains challenging. We performed\n                  <jats:italic>trans</jats:italic>\n                  expression quantitative trait locus (\n                  <jats:italic>trans</jats:italic>\n                  -eQTL) meta-analysis in 3,734 lymphoblastoid cell line samples, identifying four robust loci that replicated in an independent multi-ethnic dataset of 682 individuals. We prioritised a missense variant in the ubiquitin specific peptidase 18 (\n                  <jats:italic>USP18)</jats:italic>\n                  gene that is a known negative regulator of interferon signalling and has previously been associated with increased risk of systemic lupus erythematosus (SLE). The SLE risk allele increased the expression of 50 interferon-inducible genes, suggesting that the risk allele impairs USP18’s ability to effectively limit the interferon response. Intriguingly, the\n                  <jats:italic>USP18 trans</jats:italic>\n                  -eQTL signal would not have been discovered in a meta-analysis of up to 43,301 whole blood samples, reaffirming the importance of capturing context-specific genetic effects for GWAS interpretation.\n                </jats:p>","is_dataset_classified":null,"base_score":1.0986122886681096,"endowment":1.0986122886681096,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"19767382","pmcid":null,"openalex_id":"https://openalex.org/W4400676785","authors":[],"funders":[{"funder_name":"Swiss National Science Foundation","grant_id":"152724","title":null},{"funder_name":"Swiss National Science Foundation","grant_id":"310030","title":null},{"funder_name":"Wellcome Trust","grant_id":"unidentified","title":"unidentified"},{"funder_name":"European Commission","grant_id":"825775","title":"Common Infrastructure for National Cohorts in Europe, Canada, and Africa"}],"total_grants":4,"fwci":null,"citation_percentile":null,"influential_citations":0,"citation_trend":[{"year":2024,"count":1},{"year":2025,"count":1}],"oa_status":"green","license":"cc-by","oa_locations":[{"url":"https://www.medrxiv.org/content/medrxiv/early/2024/07/26/2024.07.15.24310442.full.pdf","host_type":"repository"},{"url":"https://www.medrxiv.org/content/medrxiv/early/2024/07/26/2024.07.15.24310442.full.pdf","host_type":"repository"},{"url":"https://syndication.highwire.org/content/doi/10.1101/2024.07.15.24310442","host_type":"publisher"},{"url":"https://doi.org/10.1101/2024.07.15.24310442","host_type":"repository"},{"url":"https://europepmc.org/article/PPR/PPR881504","host_type":"Europe_PMC"},{"url":"https://europepmc.org/api/fulltextRepo?pprId=PPR881504&type=FILE&fileName=EMS197600-pdf.pdf&mimeType=application/pdf","host_type":"Europe_PMC"},{"url":"https://doi.org/10.1038/s41467-025-63856-7","host_type":""},{"url":"https://pubmed.ncbi.nlm.nih.gov/41038828","host_type":""},{"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC12491431/","host_type":""},{"url":"https://pubmed.ncbi.nlm.nih.gov/41038828/","host_type":""},{"url":"https://research.rug.nl/en/publications/20583e0a-c598-41e6-b5d9-042b1a191bf1","host_type":""},{"url":"https://hdl.handle.net/11370/20583e0a-c598-41e6-b5d9-042b1a191bf1","host_type":""},{"url":"http://dx.doi.org/10.13039/501100000265","host_type":""},{"url":"http://dx.doi.org/10.13039/501100000780","host_type":""},{"url":"https://api.elsevier.com/content/abstract/scopus_id/105017726427","host_type":""},{"url":"http://dx.doi.org/10.13039/501100000883","host_type":""},{"url":"http://hdl.handle.net/10261/413602","host_type":""},{"url":"http://dx.doi.org/10.13039/100004440","host_type":""},{"url":"http://dx.doi.org/10.13039/501100005739","host_type":""}],"fields_of_study":["Systemic Lupus Erythematosus Research","interferon and immune responses","Atherosclerosis and Cardiovascular Diseases","0301 basic medicine","03 medical and health sciences"],"mesh_terms":[],"keywords":["Expression quantitative trait loci","Biology","Locus (genetics)","Genetics","Genome-wide association study","Allele","Quantitative trait locus","Gene","Genetic association","Single-nucleotide polymorphism","Genotype","Quantitative Trait Loci","Chromosome Mapping","Polymorphism, Single Nucleotide","Article","Cell Line","Humans","Lupus Erythematosus, Systemic","Genetic Predisposition to Disease","Interferons","Ubiquitin Thiolesterase","Alleles"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"geo"},{"name":"reactome"},{"name":"refsnp"},{"name":"arrayexpress"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-06T21:34:24.861746Z","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":[]}