{"doi":"10.1101/2020.02.24.962688","title":"IFN-λ4 is associated with increased risk and earlier occurrence of gastrointestinal, respiratory and malarial infections in Malian children","abstract":"ABSTRACT Genetic polymorphisms within the IFNL3 / IFNL4 genomic region, which encodes type III interferons, have been strongly associated with impaired clearance of hepatitis C virus (HCV) infection. We hypothesized that type III interferons might be important for the immune response to other pathogens as well. In a cohort of 914 Malian children, we analyzed episodes of malaria, gastrointestinal and respiratory infections using information for 30,626 clinic visits from birth through up to 5 years of follow-up. Genetic polymorphisms IFNL4 -rs368234815 and IFNL3 -rs4803217 that functionally affect type III interferons were genotyped with TaqMan assays. For both genetic variants and each infection, we evaluated time-to-first episode and calculated odds ratios (ORs) for the risk of an infection episode during follow-up, controlling for relevant covariates. Compared to children with the rs368234815-TT/TT genotype (IFN-λ4-Null), each copy of the rs368234815-dG allele was associated with an earlier first episode of a gastrointestinal infection (p=0.003) and respiratory infection (p=0.045). The risk of experiencing an infection episode during the follow-up was also significantly increased with each copy of the rs368234815-dG allele – for gastrointestinal infections (OR=1.53, 95%CI (1.13-2.07), p=0.005) and malaria (OR=1.30, 95%CI (1.02-1.65), p=0.033). IFNL4 -rs368234815 and IFNL3 -rs4803217 were in moderate linkage disequilibrium in this population (r 2 =0.78), and all the associations for rs4803217 were weaker and lost significance after adjusting for rs368234815, implicating IFN-λ4 and not IFN-λ3 as the primary cause of these associations. We conclude that the ability to produce IFN-λ4 may have broad health-related implications by negatively affecting the immune response and clinical outcomes of several common infections.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":122591,"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":0.9615,"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":414999,"name":"Robert Morrison","orcid":null,"position":1,"is_corresponding":false},{"id":239085,"name":"Adeola Obajemu","orcid":null,"position":2,"is_corresponding":false},{"id":448175,"name":"Almahamoudou Mahamar","orcid":null,"position":3,"is_corresponding":false},{"id":521958,"name":"Sungduk Kim","orcid":"0000-0002-7985-7204","position":4,"is_corresponding":false},{"id":565229,"name":"Oumar Attaher","orcid":null,"position":5,"is_corresponding":false},{"id":237163,"name":"Oscar Flórez-Vargas","orcid":"0000-0002-4393-2612","position":6,"is_corresponding":false},{"id":565230,"name":"Youssoufa Sidibé","orcid":null,"position":7,"is_corresponding":false},{"id":237158,"name":"Olusegun O. Onabajo","orcid":"0000-0001-6342-2380","position":8,"is_corresponding":false},{"id":378941,"name":"Amy Hutchinson","orcid":"0000-0002-4962-2711","position":9,"is_corresponding":false},{"id":449975,"name":"Michelle Manning","orcid":null,"position":10,"is_corresponding":false},{"id":564284,"name":"Jennifer Kwan","orcid":"0000-0002-7176-6340","position":11,"is_corresponding":false},{"id":515295,"name":"Nathan Brand","orcid":"0000-0003-0405-3364","position":12,"is_corresponding":false},{"id":334203,"name":"Alassane Dicko","orcid":"0000-0003-2153-8427","position":13,"is_corresponding":false},{"id":285307,"name":"Michal Fried","orcid":"0000-0002-5478-6526","position":14,"is_corresponding":false},{"id":329158,"name":"Paul S. Albert","orcid":"0000-0003-1658-1068","position":15,"is_corresponding":false},{"id":304255,"name":"Sam M. Mbulaiteye","orcid":"0000-0002-8273-9831","position":16,"is_corresponding":false},{"id":236042,"name":"Patrick E. Duffy","orcid":"0000-0002-4483-5005","position":17,"is_corresponding":false},{"id":237171,"name":"Ludmila Prokunina‐Olsson","orcid":"0000-0002-9622-2091","position":0,"is_corresponding":true}],"reference_count":33,"raw_metadata":null,"created_at":"2026-07-18T23:14:55.385653Z","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":[]}