{"doi":"10.1093/infdis/jiaa677","title":"A Multiancestry Sex-Stratified Genome-Wide Association Study of Spontaneous Clearance of Hepatitis C Virus","abstract":"BACKGROUND: Spontaneous clearance of acute hepatitis C virus (HCV) infection is more common in women than in men, independent of known risk factors. METHODS: To identify sex-specific genetic loci, we studied 4423 HCV-infected individuals (2903 male, 1520 female) of European, African, and Hispanic ancestry. We performed autosomal, and X chromosome sex-stratified and combined association analyses in each ancestry group. RESULTS: A male-specific region near the adenosine diphosphate-ribosylation factor-like 5B (ARL5B) gene was identified. Individuals with the C allele of rs76398191 were about 30% more likely to have chronic HCV infection than individuals with the T allele (OR, 0.69; P = 1.98 × 10-07), and this was not seen in females. The ARL5B gene encodes an interferon-stimulated gene that inhibits immune response to double-stranded RNA viruses. We also identified suggestive associations near septin 6 and ribosomal protein L39 genes on the X chromosome. In box sexes, allele G of rs12852885 was associated with a 40% increase in HCV clearance compared with the A allele (OR, 1.4; P = 2.46 × 10-06). Septin 6 facilitates HCV replication via interaction with the HCV NS5b protein, and ribosomal protein L39 acts as an HCV core interactor. CONCLUSIONS: These novel gene associations support differential mechanisms of HCV clearance between the sexes and provide biological targets for treatment or vaccine development.","journal":"The Journal of Infectious Diseases","year":2020,"id":107640,"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":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.801,"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":514726,"name":"Ana Valencia","orcid":"0000-0001-9133-218X","position":1,"is_corresponding":false},{"id":414209,"name":"Chloe L. 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Kirk","orcid":"0000-0002-7829-1405","position":10,"is_corresponding":false},{"id":379901,"name":"Arthur Y Kim","orcid":null,"position":11,"is_corresponding":false},{"id":331565,"name":"Georg M. Lauer","orcid":"0000-0002-9792-4271","position":12,"is_corresponding":false},{"id":270866,"name":"Raymond T. Chung","orcid":"0000-0001-7587-718X","position":13,"is_corresponding":false},{"id":355240,"name":"Andrea L. Cox","orcid":"0000-0002-9331-2462","position":14,"is_corresponding":false},{"id":447013,"name":"Marion G. Peters","orcid":"0000-0002-1484-4752","position":15,"is_corresponding":false},{"id":488177,"name":"Salim I. 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Wojcik","orcid":"0000-0001-7206-8088","position":25,"is_corresponding":false},{"id":25024,"name":"Margaret A. Taub","orcid":"0000-0001-8008-618X","position":26,"is_corresponding":false},{"id":237962,"name":"David L. 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