Evidence map›Paper›PMID 37165447›Full record

ArticleGenome medicine2023

Sex differences in the polygenic architecture of hearing problems in adults.

Flavio De Angelis, Oana A Zeleznik, Frank R Wendt, Gita A Pathak, Daniel S Tylee, Antonella De Lillo, Dora Koller, Brenda Cabrera-Mendoza, Royce E Clifford, Adam X Maihofer and 4 more

Open access · goldAbstract read
In one paragraph

Article in Genome medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed, 1 pooled it
3.9field-weighted citation impact, top 6% 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

15 citing papers in PubMed, 1 synthesis or guideline pooled it, 19 citations in OpenAlex.

  1. Pooled it
  2. Review
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  12. Pharmacological Approaches to Hearing Loss.Pharmacological reviews · 2024
    Review
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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

14 authors at 4 institutions in 3 countries.

Flavio De AngelisDepartment of Psychiatry, Yale University School of Medicine, 60 Temple, Suite 7A, New Haven, CT, USA.
Oana A ZeleznikChanning Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.
Frank R WendtDepartment of Psychiatry, Yale University School of Medicine, 60 Temple, Suite 7A, New Haven, CT, USA.
Gita A PathakDepartment of Psychiatry, Yale University School of Medicine, 60 Temple, Suite 7A, New Haven, CT, USA.
Daniel S TyleeDepartment of Psychiatry, Yale University School of Medicine, 60 Temple, Suite 7A, New Haven, CT, USA.
Antonella De LilloDepartment of Psychiatry, Yale University School of Medicine, 60 Temple, Suite 7A, New Haven, CT, USA.
Dora KollerDepartment of Psychiatry, Yale University School of Medicine, 60 Temple, Suite 7A, New Haven, CT, USA.
Brenda Cabrera-MendozaDepartment of Psychiatry, Yale University School of Medicine, 60 Temple, Suite 7A, New Haven, CT, USA.
Royce E CliffordDivision of Otolaryngology, Department of Surgery, University of California, San Diego, La Jolla, CA, USA.
Adam X MaihoferResearch Service, Veterans Affairs San Diego Healthcare System, San Diego, CA, USA.
Caroline M NievergeltResearch Service, Veterans Affairs San Diego Healthcare System, San Diego, CA, USA.
Gary C CurhanChanning Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.
Sharon G CurhanChanning Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.
Renato PolimantiDepartment of Psychiatry, Yale University School of Medicine, 60 Temple, Suite 7A, New Haven, CT, USA. renato.polimanti@yale.edu.ORCID 0000-0003-0745-6046
Yale University · USBrigham and Women's Hospital · USUniversity of California San Diego · USUniversity of Rome Tor Vergata · IT

Funding

Yale Clinical and Translational Science Award (U Component)UL1TR001863 · NCATS · YALE UNIVERSITY · PI John H. Krystal, LUCILA OHNO-MACHADO · 2016 to 2026
$102.9M
Life Course Cancer Epidemiology Cohort in WomenU01CA176726 · NCI · HARVARD UNIVERSITY D/B/A HARVARD SCHOOL OF PUBLIC HEALTH · PI ELIASSEN, A. HEATHER, WILLETT, WALTER C. · 2018 to 2025
$22.4M
Long Term Multidisciplinary Study of Cancer in Women: The Nurses Health StudyUM1CA186107 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI ELIASSEN, A. HEATHER, STAMPFER, MEIR · 2014 to 2023
$22.3M
Cancer Epidemiology Cohort in Male Health ProfessionalsU01CA167552 · NCI · HARVARD UNIVERSITY D/B/A HARVARD SCHOOL OF PUBLIC HEALTH · PI Lorelei Mucci, Walter C. Willett · 2017 to 2026
$17.0M
Risk Factors for Hearing LossU01DC010811 · NIDCD · BRIGHAM AND WOMEN'S HOSPITAL · PI CURHAN, GARY C. · 2011 to 2018
$4.0M
Investigating the Systems Genetics of the Patterns of Polysubstance Abuse and AddictionR33DA047527 · NIDA · YALE UNIVERSITY · PI POLIMANTI, RENATO · 2021 to 2023
$2.0M
Genome-wide Investigation of the Interplay Between Age-Related Hearing Loss and Smoking BehaviorsR21DC018098 · NIDCD · YALE UNIVERSITY · PI POLIMANTI, RENATO · 2019 to 2021
$440k
Decoding the Sex-Specific Biological Mechanisms of Psychiatric Disorders Using Genome-Wide AnalysesF32MH122058 · NIMH · YALE UNIVERSITY · PI WENDT, FRANK · 2020 to 2021
$118k
BLRD VA I01 BX005920NCATS NIH HHS UL1 TR001863NCI NIH HHS U01 CA167552NCI NIH HHS U01 CA176726NCI NIH HHS UM1 CA186107NIDA NIH HHS R33 DA047527NIDCD NIH HHS R21 DC018098NIDCD NIH HHS U01 DC010811NIMH NIH HHS F32 MH122058
6 · The paper itself

Abstract

backgroundHearing problems (HP) in adults are common and are associated with several comorbid conditions. Its prevalence increases with age, reflecting the cumulative effect of environmental factors and genetic predisposition. Although several risk loci have been already identified, HP biology and epidemiology are still insufficiently investigated by large-scale genetic studies.

methodsLeveraging the UK Biobank, the Nurses' Health Studies (I and II), the Health Professionals Follow-up Study, and the Million Veteran Program, we conducted a comprehensive genome-wide investigation of HP in 748,668 adult participants (discovery N = 501,825; replication N = 226,043; cross-ancestry replication N = 20,800). We leveraged the GWAS findings to characterize HP polygenic architecture, exploring sex differences, polygenic risk across ancestries, tissue-specific transcriptomic regulation, cause-effect relationships with genetically correlated traits, and gene interactions with HP environmental risk factors.

resultsWe identified 54 risk loci and demonstrated that HP polygenic risk is shared across ancestry groups. Our transcriptomic regulation analysis highlighted the potential role of the central nervous system in HP pathogenesis. The sex-stratified analyses showed several additional associations related to peripheral hormonally regulated tissues reflecting a potential role of estrogen in hearing function. This evidence was supported by the multivariate interaction analysis that showed how genes involved in brain development interact with sex, noise pollution, and tobacco smoking in relation to their HP associations. Additionally, the genetically informed causal inference analysis showed that HP is linked to many physical and mental health outcomes.

conclusionsThe results provide many novel insights into the biology and epidemiology of HP in adults. Our sex-specific analyses and transcriptomic associations highlighted molecular pathways that may be targeted for drug development or repurposing. Additionally, the potential causal relationships identified may support novel preventive screening programs to identify individuals at risk.

Indexed as

Genetic Predisposition to DiseaseSex CharacteristicsAdultFemaleFollow-Up StudiesGenome-Wide Association StudyHearingHumansMaleMultifactorial InheritanceAncestry; Polygenic risk scoresCausal inferenceGenome-wide association studyGenome-wide gene-by-environment interactionHearing problemsPleiotropySex differencesTranscriptomic regulation

Identifiers

PMID37165447
PMCPMC10173489
OpenAlexW4376132003

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

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 Socratic graph.