Evidence map›Paper›PMID 33119750›Full record

ArticleThe Journal of infectious diseases2021

A Multiancestry Sex-Stratified Genome-Wide Association Study of Spontaneous Clearance of Hepatitis C Virus.

Candelaria Vergara, Ana Valencia, Chloe L Thio, James J Goedert, Alessandra Mangia, Valeria Piazzolla, Eric Johnson, Alex H Kral, Thomas R O'Brien, Shruti H Mehta and 19 more

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of infectious diseases, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
0.5field-weighted citation impact, top 34% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed, 6 citations in OpenAlex.

  1. Article
  2. Review
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  5. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

29 authors at 13 institutions in 5 countries.

Candelaria VergaraJohns Hopkins University, Bloomberg School of Public Health, Baltimore, Maryland, USA.ORCID 0000-0003-3297-8057
Ana ValenciaJohns Hopkins University, School of Medicine, Baltimore, Maryland, USA.
Chloe L ThioJohns Hopkins University, School of Medicine, Baltimore, Maryland, USA.
James J GoedertDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
Alessandra MangiaLiver Unit IRCCS "Casa Sollievo della Sofferenza," San Giovanni Rotondo, Italy.
Valeria PiazzollaLiver Unit IRCCS "Casa Sollievo della Sofferenza," San Giovanni Rotondo, Italy.
Eric JohnsonRTI International, Research Triangle Park, North Carolina, USA.
Alex H KralRTI International, Research Triangle Park, North Carolina, USA.
Thomas R O'BrienDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
Shruti H MehtaJohns Hopkins University, Bloomberg School of Public Health, Baltimore, Maryland, USA.
Gregory D KirkJohns Hopkins University, Bloomberg School of Public Health, Baltimore, Maryland, USA.
Arthur Y KimDivision of Infectious Diseases, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Georg M LauerLiver Center and Gastrointestinal Division, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Raymond T ChungLiver Center and Gastrointestinal Division, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Andrea L CoxJohns Hopkins University, Bloomberg School of Public Health, Baltimore, Maryland, USA.
Marion G PetersDivision of Gastroenterology, Department of Medicine, School of Medicine, University of California, San Francisco, California, USA.
Salim I KhakooUniversity of Southampton, Southampton General Hospital, Southampton, United Kingdom.
Laurent AlricDepartment of Internal Medicine and Digestive Diseases, CHU Rangueil, UMR 152 IRD, Toulouse 3 University, France.
Matthew E CrampSouth West Liver Unit, Plymouth, United Kingdom.
Sharyne M DonfieldRho, Inc., Chapel Hill, North Carolina, USA.
Brian R EdlinSUNY Downstate College of Medicine, Brooklyn, New York, USA.
Michael P BuschUniversity of California and Vitalant Research Institute, San Francisco, California, USA.
Graeme AlexanderUCL Institute for Liver and Digestive Health, Royal Free Hospital, Hampstead, London, United Kingdom.
Hugo R RosenUniversity of Colorado, Aurora, Colorado, USA.
Edward L MurphyUniversity of California and Vitalant Research Institute, San Francisco, California, USA.
Genevieve L WojcikJohns Hopkins University, Bloomberg School of Public Health, Baltimore, Maryland, USA.
Margaret A TaubJohns Hopkins University, Bloomberg School of Public Health, Baltimore, Maryland, USA.
David L ThomasJohns Hopkins University, School of Medicine, Baltimore, Maryland, USA.
Priya DuggalJohns Hopkins University, School of Medicine, Baltimore, Maryland, USA.
Johns Hopkins University · USHarvard University · USCasa Sollievo della Sofferenza · ITNational Institutes of Health · USPacific Research Institute · USRTI International · USHôpital Rangueil · FRRho (United States) · USSouthampton General Hospital · GBSUNY Downstate Health Sciences University · USThe Royal Free Hospital · GBUniversity of California, San Francisco · USUniversity of Colorado Anschutz Medical Campus · US

Funding

Institute for Clinical and Translational Research (UL1)UL1RR025005 · NCRR · JOHNS HOPKINS UNIVERSITY · PI FORD, DANIEL ERNEST · 2007 to 2011
$75.8M
NATURAL HISTORY OF AIDS IN HOMOSEXUAL MENU01AI035040 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI DETELS, ROGER, MARTINEZ-MAZA, OTONIEL · 1993 to 2018
$75.2M
University of Pittsburgh Multicenter AIDS Cohort Study (MACS)U01AI035041 · NIAID · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI MARTINSON, JEREMY JAMES, RINALDO, CHARLES R · 1993 to 2018
$71.4M
MULTICENTER AIDS COHORT STUDYU01AI035039 · NIAID · NORTHWESTERN UNIVERSITY AT CHICAGO · PI WOLINSKY, STEVEN M · 1993 to 2018
$66.4M
Women's Interagency HIV Study (WIHS-V)U01AI035004 · NIAID · MONTEFIORE MEDICAL CENTER (BRONX, NY) · PI ANASTOS, KATHRYN M., SHARMA, ANJALI · 1993 to 2018
$65.7M
WOMEN'S INTERAGENCY HIV STUDY ORGANIZATION, MANAGEMENT AND COMMUNICATIONSU01AI034989 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI AOUIZERAT, BRADLEY E, GREENBLATT, RUTH MARTHA · 1993 to 2018
$65.6M
Multicenter Aids Cohort Study- Part B (Baltimore Site)U01AI035042 · NIAID · JOHNS HOPKINS UNIVERSITY · PI BROWN, TODD T, MARGOLICK, JOSEPH B. · 1993 to 2018
$61.5M
Women's Interagency HIV Study (WIHS) IIIU01AI031834 · NIAID · SUNY DOWNSTATE MEDICAL CENTER · PI GUSTAFSON, DEBORAH R., MINKOFF, HOWARD · 1998 to 2018
$53.5M
WOMEN'S INTERAGENCY HIV STUDY (WIHS) ORGANIZATION AND MANAGEMENTU01AI034994 · NIAID · GEORGETOWN UNIVERSITY · PI KASSAYE, SEBLE G · 1993 to 2018
$52.0M
Women's Interagency HIV Study (WIHS) IV, Chicago ConsortiumU01AI034993 · NIAID · HEKTOEN INSTITUTE FOR MEDICAL RESEARCH · PI COHEN, MARDGE H, FRENCH, AUDREY · 1994 to 2018
$51.0M
CTSA INFRASTRUCTURE FOR PEDIATRIC RESEARCHUL1RR024996 · NCRR · WEILL MEDICAL COLL OF CORNELL UNIV · PI IMPERATO-MCGINLEY, JULIANNE L · 2007 to 2011
$49.6M
Virology CoreU19AI082630 · NIAID · MASSACHUSETTS GENERAL HOSPITAL · PI RAYMOND T CHUNG, GEORG Michael LAUER · 2009 to 2026
$48.1M
CCR NIH HHS HHSN261200800001CNCI NIH HHS HHSN261200800001ENCRR NIH HHS UL1 RR024996NCRR NIH HHS UL1 RR025005NHLBI NIH HHS R01 HL076902NIAID NIH HHS R01 AI148049NIAID NIH HHS U01 AI031834NIAID NIH HHS U01 AI034989NIAID NIH HHS U01 AI034993NIAID NIH HHS U01 AI034994NIAID NIH HHS U01 AI035004NIAID NIH HHS U01 AI035039NIAID NIH HHS U01 AI035040NIAID NIH HHS U01 AI035041NIAID NIH HHS U01 AI035042NIAID NIH HHS U01 AI035043NIAID NIH HHS U01 AI042590NIAID NIH HHS U01 AI131314NIAID NIH HHS U19 AI066345NIAID NIH HHS U19 AI082630NIAID NIH HHS U19 AI088791NICHD NIH HHS R01 HD041224NICHD NIH HHS U01 HD032632NIDA NIH HHS R01 DA013324NIDA NIH HHS R01 DA016159NIDA NIH HHS R01 DA021550NIDA NIH HHS U01 DA036297
6 · The paper itself

Abstract

backgroundSpontaneous clearance of acute hepatitis C virus (HCV) infection is more common in women than in men, independent of known risk factors.

methodsTo 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.

resultsA 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.

conclusionsThese novel gene associations support differential mechanisms of HCV clearance between the sexes and provide biological targets for treatment or vaccine development.

Indexed as

Hepatitis CSex FactorsFemaleGenome-Wide Association StudyHepacivirusHumansMalePolymorphism, Single NucleotideRibosomal ProteinsSeptinsViral Loadribosomal protein L39Ribosomal ProteinsSeptinsARL5BGWASHCVHost-geneticsimmuneinfectionSeptin 6SexX chromosome

Identifiers

PMID33119750
PMCPMC8205624
OpenAlexW3095463208

What OpenQuestion holds

Textmetadata
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.