Evidence map›Paper›PMID 32888428›Full record

ArticleAmerican journal of human genetics2020

Genome-wide Study Identifies Association between HLA-B

Kristi Krebs, Jonas Bovijn, Neil Zheng, Maarja Lepamets, Jenny C Censin, Tuuli Jürgenson, Dage Särg, Erik Abner, Triin Laisk, Yang Luo and 18 more

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Article in American journal of human genetics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed, 2 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

32 citing papers in PubMed, 2 syntheses or guidelines pooled it.

  1. Pooled it
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  13. Identifying patients at risk of anaphylaxis.The World Allergy Organization journal · 2024
    Review
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  20. Association betweenFrontiers in pharmacology · 2023
    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

28 authors.

Kristi KrebsEstonian Genome Center, Institute of Genomics, University of Tartu, Tartu 51010, Estonia; Institute of Molecular and Cell Biology, University of Tartu, Tartu 51010, Estonia.
Jonas BovijnWellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7BN, UK; Big Data Institute at the Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford OX3 7FZ, UK.
Neil ZhengDepartment of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Maarja LepametsEstonian Genome Center, Institute of Genomics, University of Tartu, Tartu 51010, Estonia; Institute of Molecular and Cell Biology, University of Tartu, Tartu 51010, Estonia.
Jenny C CensinWellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7BN, UK; Big Data Institute at the Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford OX3 7FZ, UK.
Tuuli JürgensonEstonian Genome Center, Institute of Genomics, University of Tartu, Tartu 51010, Estonia.
Dage SärgInstitute of Computer Science, University of Tartu, Tartu 51009, Estonia.
Erik AbnerEstonian Genome Center, Institute of Genomics, University of Tartu, Tartu 51010, Estonia.
Triin LaiskEstonian Genome Center, Institute of Genomics, University of Tartu, Tartu 51010, Estonia.
Yang LuoDivision of Rheumatology, Inflammation and Immunity, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA; Division of Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Biomedical Informatics, Harvard Medical School, Boston, MA 02115, USA; Center for Data Sciences, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Line SkotteDepartment of Epidemiology Research, Statens Serum Institut, Copenhagen 2300, Denmark.
Frank GellerDepartment of Epidemiology Research, Statens Serum Institut, Copenhagen 2300, Denmark.
Bjarke FeenstraDepartment of Epidemiology Research, Statens Serum Institut, Copenhagen 2300, Denmark.
Wei Wang23andMe, Inc., Sunnyvale, CA 94086, USA.
Adam Auton23andMe, Inc., Sunnyvale, CA 94086, USA.
23andMe Research Team23andMe, Inc., Sunnyvale, CA 94086, USA.
Soumya RaychaudhuriDivision of Rheumatology, Inflammation and Immunity, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA; Division of Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Biomedical Informatics, Harvard Medical School, Boston, MA 02115, USA; Center for Data Sciences, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA; Centre for Genetics and Genomics Versus Arthritis, Manchester Academic Health Science Centre, University of Manchester, Manchester M13 9PT, UK.
Tõnu EskoEstonian Genome Center, Institute of Genomics, University of Tartu, Tartu 51010, Estonia.
Andres MetspaluEstonian Genome Center, Institute of Genomics, University of Tartu, Tartu 51010, Estonia.
Sven LaurInstitute of Computer Science, University of Tartu, Tartu 51009, Estonia; STACC, Tartu 51009, Estonia.
Dan M RodenDepartment of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Department of Pharmacology, Vanderbilt University School of Medicine, TN 37232, USA.
Wei-Qi WeiDepartment of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Michael V HolmesBig Data Institute at the Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford OX3 7FZ, UK; National Institute for Health Research Oxford Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital, Oxford OX3 7LE, UK; Clinical Trial Service Unit and Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, University of Oxford, Oxford OX3 7LF, UK; Medical Research Council Population Health Research Unit (MRC PHRU), Nuffield Department of Population Health, University of Oxford, Oxford OX3 7LF, UK.
Cecilia M LindgrenWellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7BN, UK; Big Data Institute at the Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford OX3 7FZ, UK; National Institute for Health Research Oxford Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital, Oxford OX3 7LE, UK; Program in Medical and Population Genetics, Broad Institute, Cambridge, MA 02142, USA.
Elizabeth J PhillipsDepartment of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Department of Pharmacology, Vanderbilt University School of Medicine, TN 37232, USA; Institute for Immunology & Infectious Diseases, Murdoch University, Murdoch, WA 6150, Australia.
Reedik MägiEstonian Genome Center, Institute of Genomics, University of Tartu, Tartu 51010, Estonia.
Lili MilaniEstonian Genome Center, Institute of Genomics, University of Tartu, Tartu 51010, Estonia. Electronic address: lili.milani@ut.ee.
João FadistaDepartment of Epidemiology Research, Statens Serum Institut, Copenhagen 2300, Denmark; Department of Clinical Sciences, Lund University Diabetes Centre, 214 28 Malmö, Sweden; Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki 00014, Finland.

Funding

The Vanderbilt Institute for Clinical and Translational Research (VICTR)UL1TR000445 · NCATS · VANDERBILT UNIVERSITY MEDICAL CENTER · PI BERNARD, GORDON RAPHAEL · 2012 to 2016
$41.4M
NATIENS: A Phase III Randomized Double Blinded Study to Determine the Mechanisms and Optimal Management of Stevens-Johnson Syndrome and Toxic Epidermal NecrolysisU01AI154659 · NIAID · VANDERBILT UNIVERSITY MEDICAL CENTER · PI PHILLIPS, ELIZABETH · 2020 to 2025
$15.5M
Understanding and preventing HLA-associated drug reactionsP50GM115305 · NIGMS · VANDERBILT UNIVERSITY MEDICAL CENTER · PI PHILLIPS, ELIZABETH · 2015 to 2019
$13.0M
The Genetic Determinants of Human GNRH DeficiencyP50HD028138 · NICHD · MASSACHUSETTS GENERAL HOSPITAL · PI SEMINARA, STEPHANIE BETH · 2014 to 2020
$12.9M
Genetic risk and long-term outcomes associated with Drug-induced Stevens-Johnson syndrome and toxic epidermal necrolysis in survivorsR01HG010863 · NHGRI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI PHILLIPS, ELIZABETH · 2019 to 2022
$3.1M
PheMAP: Measured, Automated Profile to Facilitate High Throughput PhenotypingR01GM139891 · NIGMS · VANDERBILT UNIVERSITY MEDICAL CENTER · PI WEI, WEI-QI · 2021 to 2024
$1.7M
Exploring Statin Pleiotropic Effects within a Very Large EHR Cohort - Diversity SupplementR01HL133786 · NHLBI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI WEI, WEI-QI · 2017 to 2020
$1.7M
Immune-mediated adverse drug reactions to HIV and TB treatments in South Africa: predict, prevent and improve long-term outcomes (IMARI SA study)R01AI152183 · NIAID · UNIVERSITY OF CAPE TOWN · PI MEINTJES, GRAEME AYTON, PHILLIPS, ELIZABETH · 2020 to 2025
$1.6M
Single Cell definition of pathogenic T cells in Drug-induced Stevens-Johnson-Syndrome/Toxic epidermal necrolysisR21AI139021 · NIAID · VANDERBILT UNIVERSITY MEDICAL CENTER · PI PHILLIPS, ELIZABETH · 2018 to 2019
$435k
NCATS NIH HHS UL1 TR000445NHGRI NIH HHS R01 HG010863NHLBI NIH HHS R01 HL133786NIAID NIH HHS R01 AI152183NIAID NIH HHS R21 AI139021NIAID NIH HHS U01 AI154659NICHD NIH HHS P50 HD028138NIGMS NIH HHS P50 GM115305NIGMS NIH HHS R01 GM139891Wellcome Trust
6 · The paper itself

Abstract

Hypersensitivity reactions to drugs are often unpredictable and can be life threatening, underscoring a need for understanding their underlying mechanisms and risk factors. The extent to which germline genetic variation influences the risk of commonly reported drug allergies such as penicillin allergy remains largely unknown. We extracted data from the electronic health records of more than 600,000 participants from the UK, Estonian, and Vanderbilt University Medical Center's BioVU biobanks to study the role of genetic variation in the occurrence of self-reported penicillin hypersensitivity reactions. We used imputed SNP to HLA typing data from these cohorts to further fine map the human leukocyte antigen (HLA) association and replicated our results in 23andMe's research cohort involving a total of 1.12 million individuals. Genome-wide meta-analysis of penicillin allergy revealed two loci, including one located in the HLA region on chromosome 6. This signal was further fine-mapped to the HLA-B

Indexed as

Polymorphism, Single NucleotideAdultAllelesArthritis, RheumatoidChromosomes, Human, Pair 6Drug HypersensitivityElectronic Health RecordsEuropeFemaleGene ExpressionGenetic LociGenetic Predisposition to DiseaseGenome, HumanGenome-Wide Association StudyHistocompatibility TestingHLA-B AntigensHLA-B55 antigenHLA-B AntigensPenicillinsProtein Tyrosine Phosphatase, Non-Receptor Type 22PTPN22 protein, human23andMeBioVuEHREstBBGWASHLA-B∗55:01penicillin allergypharmacogenomicsPTPN22UKBB

Identifiers

PMID32888428
PMCPMC7536643

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Registered trials

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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.