Evidence map›Paper›PMID 34611364›Full record

ArticleNature genetics2021

A high-resolution HLA reference panel capturing global population diversity enables multi-ancestry fine-mapping in HIV host response.

Yang Luo, Masahiro Kanai, Wanson Choi, Xinyi Li, Saori Sakaue, Kenichi Yamamoto, Kotaro Ogawa, Maria Gutierrez-Arcelus, Peter K Gregersen, Philip E Stuart and 25 more

Erratum issuedAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature genetics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 128 papers, 7 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
128citing papers in PubMed, 7 pooled it
–field-weighted citation impact
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

128 citing papers in PubMed, 7 syntheses or guidelines pooled it.

  1. Pooled it
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  16. NK-like and networked CD8bioRxiv : the preprint server for biology · 2026
    Article
  17. Article
  18. Review
  19. Shared trans-ancestry architecture of HLA-mediated disease risk in themedRxiv : the preprint server for health sciences · 2026
    Article
  20. Article

68 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

35 authors.

Yang LuoCenter for Data Sciences, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. yangluo@broadinstitute.org.ORCID http://orcid.org/0000-0001-7385-6166
Masahiro KanaiDepartment of Biomedical Informatics, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0001-5165-4408
Wanson ChoiDepartment of Biomedical Sciences, Seoul National University College of Medicine, Seoul, South Korea.
Xinyi LiCommittee on Genetics, Genomics, and Systems Biology, University of Chicago, Chicago, IL, USA.
Saori SakaueCenter for Data Sciences, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0003-3618-9717
Kenichi YamamotoDepartment of Statistical Genetics, Osaka University Graduate School of Medicine, Suita, Japan.
Kotaro OgawaDepartment of Statistical Genetics, Osaka University Graduate School of Medicine, Suita, Japan.
Maria Gutierrez-ArcelusCenter for Data Sciences, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0001-7898-7691
Peter K GregersenThe Robert S. Boas Center for Genomics and Human Genetics, Feinstein Institute for Medical Research,North Short LIJ Health System, Manhasset, NY, USA.ORCID http://orcid.org/0000-0003-1613-1518
Philip E StuartDepartment of Dermatology, University of Michigan, Ann Arbor, MI, USA.ORCID http://orcid.org/0000-0002-9546-6529
James T ElderDepartment of Dermatology, University of Michigan, Ann Arbor, MI, USA.ORCID http://orcid.org/0000-0003-4215-3294
Lukas ForerInstitute of Genetic Epidemiology, Department of Genetics and Pharmacology, Medical University of Innsbruck, Innsbruck, Austria.ORCID http://orcid.org/0000-0003-2139-7329
Sebastian SchönherrInstitute of Genetic Epidemiology, Department of Genetics and Pharmacology, Medical University of Innsbruck, Innsbruck, Austria.
Christian FuchsbergerInstitute of Genetic Epidemiology, Department of Genetics and Pharmacology, Medical University of Innsbruck, Innsbruck, Austria.ORCID http://orcid.org/0000-0002-5918-8947
Albert V SmithDepartment of Biostatistics, University of Michigan School of Public Health, Ann Arbor, MI, USA.ORCID http://orcid.org/0000-0003-1942-5845
Jacques FellayPrecision Medicine Unit, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.ORCID http://orcid.org/0000-0002-8240-939X
Mary CarringtonBasic Science Program, Frederick National Laboratory for Cancer Research, National Cancer Institute, Frederick, MD, USA.ORCID http://orcid.org/0000-0002-2692-2180
David W HaasVanderbilt University Medical Center, Nashville, TN, USA.
Xiuqing GuoThe Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, USA.
Nicholette D PalmerDepartment of Biochemistry, Wake Forest School of Medicine, Winston-Salem, NC, USA.ORCID http://orcid.org/0000-0001-8883-2511
Yii-Der Ida ChenThe Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, USA.
Jerome I RotterThe Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, USA.ORCID http://orcid.org/0000-0001-7191-1723
Kent D TaylorThe Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, USA.ORCID http://orcid.org/0000-0002-2756-4370
Stephen S RichCenter for Public Health Genomics, University of Virginia School of Medicine, Charlottesville, VA, USA.ORCID http://orcid.org/0000-0003-3872-7793
Adolfo CorreaMedicine, University of Mississippi Medical Center, Jackson, MS, USA.ORCID http://orcid.org/0000-0002-9501-600X
James G WilsonPhysiology and Biophysics, University of Mississippi Medical Center, Jackson, MS, USA.
Sekar KathiresanBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Michael H ChoChanning Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0002-4907-1657
Andres MetspaluEstonian Genome Center, Institute of Genomics, University of Tartu, Tartu, Estonia.ORCID http://orcid.org/0000-0002-3718-796X
Tonu EskoBroad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0003-1982-6569
Yukinori OkadaDepartment of Statistical Genetics, Osaka University Graduate School of Medicine, Suita, Japan.ORCID http://orcid.org/0000-0002-0311-8472
Buhm HanDepartment of Biomedical Sciences, Seoul National University College of Medicine, Seoul, South Korea.ORCID http://orcid.org/0000-0002-2266-5164
NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium
Paul J McLarenJ.C. Wilt Infectious Diseases Research Centre, National Microbiology Laboratories, Public Health Agency of Canada, Winnipeg, Manitoba, Canada.ORCID http://orcid.org/0000-0001-6019-7018
Soumya RaychaudhuriCenter for Data Sciences, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. soumya@broadinstitute.org.ORCID http://orcid.org/0000-0002-1901-8265

Funding

Leadership and Operations Center (LOC), AIDS Clinical Trials Group (ACTG); LOC 1/UM1AI068636 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Joseph J Eron, RAJESH T GANDHI · 2011 to 2026
$1073.1M
Statistical and Data Management Center (SDMC), AIDS Clinical Trials Group (ACTG)UM1AI068634 · NIAID · HARVARD UNIVERSITY D/B/A HARVARD SCHOOL OF PUBLIC HEALTH · PI Marlene Ann Cooper, Michael David Hughes · 2011 to 2026
$246.6M
WOMEN'S HEALTH AGENDAU01AI038858 · NIAID · SOCIAL AND SCIENTIFIC SYSTEMS, INC. · PI BENSON, CONSTANCE ANN · 1996 to 2008
$157.5M
AIDS Clinical Trials Group NetworkU01AI068636 · NIAID · SOCIAL AND SCIENTIFIC SYSTEMS, INC. · PI KURITZKES, DANIEL R. · 2006 to 2010
$147.1M
UCLA Clinical Translational Science InstituteUL1TR001881 · NCATS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ARLEEN F. BROWN, ARASH NAEIM · 2016 to 2026
$118.1M
Validation, CLIA and Qualification (VQC): Enhancing the RS ratio as a tool for AIDS Clinical Trial Group (ACTG) tuberculosis trialsUM1AI106701 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Grace M Aldrovandi · 2014 to 2026
$116.8M
The impact of HIV viral diversity and cellular immunity on HIV pathogenesisP30AI060354 · NIAID · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI RAJESH T GANDHI · 2004 to 2026
$94.4M
Virus & Reservoirs CoreP30AI045008 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI DAVID S METZGER · 1999 to 2026
$78.6M
Engaging University of California Stakeholders for Biorespository ResearchUL1TR000004 · NCATS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI GRANDIS, JENNIFER RUBIN · 2012 to 2015
$78.0M
Virology, Immunology, and Microbiology CoreP30AI050410 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI DAVID M. MARGOLIS · 2001 to 2026
$76.9M
ZONA-FREE HAMSTER OVA ASSAY AS AN INDICATOR OF MALE FERTILITYM01RR000425 · NCRR · LUNDQUIST INSTITUTE FOR BIOMEDICAL INNOVATION AT HARBOR-UCLA MEDICAL CENTER · PI ANDERSON, GAIL V · 1985 to 2011
$74.2M
Virology and Molecular Biomarkers CoreP30AI050409 · NIAID · EMORY UNIVERSITY · PI Ann M Chahroudi, Colleen F Kelley · 2002 to 2026
$74.0M
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6 · The paper itself

Abstract

Fine-mapping to plausible causal variation may be more effective in multi-ancestry cohorts, particularly in the MHC, which has population-specific structure. To enable such studies, we constructed a large (n = 21,546) HLA reference panel spanning five global populations based on whole-genome sequences. Despite population-specific long-range haplotypes, we demonstrated accurate imputation at G-group resolution (94.2%, 93.7%, 97.8% and 93.7% in admixed African (AA), East Asian (EAS), European (EUR) and Latino (LAT) populations). Applying HLA imputation to genome-wide association study data for HIV-1 viral load in three populations (EUR, AA and LAT), we obviated effects of previously reported associations from population-specific HIV studies and discovered a novel association at position 156 in HLA-B. We pinpointed the MHC association to three amino acid positions (97, 67 and 156) marking three consecutive pockets (C, B and D) within the HLA-B peptide-binding groove, explaining 12.9% of trait variance.

Indexed as

Genetics, PopulationGenetic VariationPhysical Chromosome MappingAllelesAmino AcidsGene FrequencyHaplotypesHIV-1HIV InfectionsHLA AntigensHost-Pathogen InteractionsHumansLinkage DisequilibriumReference StandardsSelection, GeneticViral LoadAmino AcidsHLA Antigens

Identifiers

PMID34611364
PMCPMC8959399

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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.