Evidence map›Paper›PMID 32929111›Full record

ArticleScientific reports2020

Multi-omic studies on missense PLG variants in families with otitis media.

Tori C Bootpetch, Lena Hafrén, Christina L Elling, Erin E Baschal, Ani W Manichaikul, Harold S Pine, Wasyl Szeremeta, Melissa A Scholes, Stephen P Cass, Eric D Larson and 26 more

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

Article in Scientific reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
0.7field-weighted citation impact, top 29% 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

7 citing papers in PubMed, 8 citations in OpenAlex.

  1. Article
  2. Rare and low-frequency variants in families with otitis media.Journal of molecular medicine (Berlin, Germany) · 2025
    Article
  3. Article
  4. Review
  5. Article
  6. Microbiota Associated With Cholesteatoma Tissue in Chronic Suppurative Otitis Media.Frontiers in cellular and infection microbiology · 2022
    Article
  7. The role of CDHR3 in susceptibility to otitis media.Journal of molecular medicine (Berlin, Germany) · 2021
    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

36 authors at 12 institutions in 5 countries.

Tori C BootpetchDepartment of Otolaryngology-Head and Neck Surgery, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Lena HafrénDepartment of Otorhinolaryngology, Head and Neck Surgery, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
Christina L EllingDepartment of Otolaryngology-Head and Neck Surgery, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Erin E BaschalDepartment of Otolaryngology-Head and Neck Surgery, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Ani W ManichaikulCenter for Public Health Genomics, School of Medicine, University of Virginia, Charlottesville, VA, USA.
Harold S PineDepartment of Otolaryngology, University of Texas Medical Branch, Galveston, TX, USA.
Wasyl SzeremetaDepartment of Otolaryngology, University of Texas Medical Branch, Galveston, TX, USA.
Melissa A ScholesDepartment of Otolaryngology-Head and Neck Surgery, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Stephen P CassDepartment of Otolaryngology-Head and Neck Surgery, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Eric D LarsonDepartment of Otolaryngology-Head and Neck Surgery, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Kenny H ChanDepartment of Otolaryngology-Head and Neck Surgery, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Rafaqat IshaqDepartment of Otorhinolaryngology, Head and Neck Surgery, School of Medicine, University of Maryland, Baltimore, MD, USA.
Jeremy D PragerDepartment of Otolaryngology-Head and Neck Surgery, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Rehan S ShaikhDepartment of Otorhinolaryngology, Head and Neck Surgery, School of Medicine, University of Maryland, Baltimore, MD, USA.
Samuel P GubbelsDepartment of Otolaryngology-Head and Neck Surgery, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Ayesha YousafInstitute of Molecular Biology and Biotechnology, Bahauddin Zakariya University, Multan, Punjab, Pakistan.
University of Washington Center for Mendelian Genomics (UW-CMG)
Todd M WineDepartment of Otolaryngology-Head and Neck Surgery, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Michael J BamshadDepartment of Genome Sciences, University of Washington, Seattle, WA, USA.
Patricia J YoonDepartment of Otolaryngology-Head and Neck Surgery, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Herman A JenkinsDepartment of Otolaryngology-Head and Neck Surgery, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Deborah A NickersonDepartment of Genome Sciences, University of Washington, Seattle, WA, USA.
Sven-Olrik StreubelDepartment of Otolaryngology-Head and Neck Surgery, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Norman R FriedmanDepartment of Otolaryngology-Head and Neck Surgery, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Daniel N FrankDivision of Infectious Diseases, Department of Medicine, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Elisabet EinarsdottirFolkhälsan Institute of Genetics and Molecular Neurology Research Program, University of Helsinki, Helsinki, Finland.
Juha KereFolkhälsan Institute of Genetics and Molecular Neurology Research Program, University of Helsinki, Helsinki, Finland.
Saima RiazuddinDepartment of Otorhinolaryngology, Head and Neck Surgery, School of Medicine, University of Maryland, Baltimore, MD, USA.
Kathleen A DalyDepartment of Otolaryngology, Head and Neck Surgery, University of Minnesota, Minneapolis, MN, USA.
Suzanne M LealDepartment of Neurology, Center for Statistical Genetics, Gertrude H. Sergievsky Center, Taub Institute for Alzheimer's Disease and the Aging Brain, Columbia University Medical Center, New York, NY, USA.
Allen F RyanDivision of Otolaryngology, Department of Surgery, UCSD School of Medicine and VA Medical Center, La Jolla, CA, USA.
Petri S MattilaDepartment of Otorhinolaryngology, Head and Neck Surgery, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
Zubair M AhmedDepartment of Otorhinolaryngology, Head and Neck Surgery, School of Medicine, University of Maryland, Baltimore, MD, USA.
Michele M SaleCenter for Public Health Genomics, School of Medicine, University of Virginia, Charlottesville, VA, USA.
Tasnee ChonmaitreeDivision of Infectious Diseases, Department of Pediatrics, University of Texas Medical Branch, Galveston, TX, USA.
Regie Lyn P Santos-CortezDepartment of Otolaryngology-Head and Neck Surgery, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA. regie.santos-cortez@cuanschutz.edu.
University of Colorado Anschutz Medical Campus · USChildren's Hospital Colorado · USUniversity of Maryland, Baltimore · USUniversity of Washington · USThe University of Texas Medical Branch at Galveston · USColumbia University Irving Medical Center · USHelsinki University Hospital · FIKarolinska Institutet · SEUniversity of Virginia · USBahauddin Zakariya University · PKCenter for Children · USUniversity of Minnesota · US

Funding

UW Center for Mendelian GenomicsUM1HG006493 · NHGRI · UNIVERSITY OF WASHINGTON · PI BAMSHAD, MICHAEL JOSEPH, LEAL, SUZANNE M · 2016 to 2020
$15.3M
NHGRI Genome Sequencing Program Coordinating CenterU24HG008956 · NHGRI · RUTGERS, THE STATE UNIV OF N.J. · PI BUYSKE, STEVEN G, MATISE, TARA C. · 2016 to 2020
$4.9M
Institutional Training in Otolaryngology ResearchT32DC012280 · NIDCD · UNIVERSITY OF COLORADO DENVER · PI Yuri Agrawal, Sue C. Kinnamon · 2013 to 2026
$3.4M
Otitis Media Susceptibility and Middle Ear Microbial Shifts due to Gene VariantsR01DC015004 · NIDCD · UNIVERSITY OF COLORADO DENVER · PI SANTOS-CORTEZ, REGIE LYN PASTOR · 2016 to 2020
$1.9M
NHGRI NIH HHS U24 HG008956NHGRI NIH HHS UM1 HG006493NIDCD NIH HHS R01 DC015004NIDCD NIH HHS T32 DC012280NIH HHS U24 HG008956
6 · The paper itself

Abstract

Otitis media (OM), a very common disease in young children, can result in hearing loss. In order to potentially replicate previously reported associations between OM and PLG, exome and Sanger sequencing, RNA-sequencing of saliva and middle ear samples, 16S rRNA sequencing, molecular modeling, and statistical analyses including transmission disequilibrium tests (TDT) were performed in a multi-ethnic cohort of 718 families and simplex cases with OM. We identified four rare PLG variants c.112A > G (p.Lys38Glu), c.782G > A (p.Arg261His), c.1481C > T (p.Ala494Val) and c.2045 T > A (p.Ile682Asn), and one common variant c.1414G > A (p.Asp472Asn). However TDT analyses for these PLG variants did not demonstrate association with OM in 314 families. Additionally PLG expression is very low or absent in normal or diseased middle ear in mouse and human, and salivary expression and microbial α-diversity were non-significant in c.1414G > A (p.Asp472Asn) carriers. Based on molecular modeling, the novel rare variants particularly c.782G > A (p.Arg261His) and c.2045 T > A (p.Ile682Asn) were predicted to affect protein structure. Exploration of other potential disease mechanisms will help elucidate how PLG contributes to OM susceptibility in humans. Our results underline the importance of following up findings from genome-wide association through replication studies, preferably using multi-omic datasets.

Indexed as

Mutation, MissenseAnimalsEar, MiddleFemaleGenomicsHumansMaleMiceMicrobiotaOtitis MediaPedigreePlasminogenPolymorphism, Single NucleotideSalivaPlasminogen

Identifiers

PMID32929111
PMCPMC7490366
OpenAlexW3085146878

What Socratic holds

Textmetadata
LicenceCC BY
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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 Socratic graph.