Evidence map›Paper›PMID 39999848›Full record

ArticleAmerican journal of human genetics2025

Identification of genes associated with testicular germ cell tumor susceptibility through a transcriptome-wide association study.

Emilio Ugalde-Morales, Rona Wilf, John Pluta, Alexander Ploner, Mengyao Fan, Mohammad Damra, Katja K Aben, Lynn Anson-Cartwright, Chu Chen, Victoria K Cortessis and 40 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in American journal of human genetics, 2025. 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
–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

7 citing papers in PubMed.

  1. Overlapping genetic etiology of pediatric and adult germ cell tumors.Journal of the National Cancer Institute · 2026
    Article
  2. Article
  3. Family-Based Study RevealsInternational journal of molecular sciences · 2026
    Article
  4. Article
  5. Article
  6. Article
  7. 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

50 authors.

Emilio Ugalde-MoralesDepartment of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden.
Rona WilfDivision of Translational Medicine and Human Genetics, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
John PlutaDivision of Translational Medicine and Human Genetics, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Alexander PlonerDepartment of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden.
Mengyao FanDivision of Translational Medicine and Human Genetics, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Mohammad DamraDivision of Translational Medicine and Human Genetics, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Katja K AbenNetherlands Comprehensive Cancer Organization, Radboud University Medical Center, Utrecht, the Netherlands; Radboud University Medical Center, Nijmegen, the Netherlands.
Lynn Anson-CartwrightDepartment of Surgery (Urology), University of Toronto and The Princess Margaret Cancer Centre, Toronto, ON, Canada.
Chu ChenEpidemiology Program, Fred Hutchinson Cancer Center, Seattle, WA, USA; Department of Epidemiology, University of Washington, Seattle, WA, USA.
Victoria K CortessisDepartments of Preventive Medicine and Obstetrics and Gynecology, Keck School of Medicine at the University of Southern California, Los Angeles, CA, USA.
Siamak DaneshmandDepartments of Urology, Keck School of Medicine at the University of Southern California, Los Angeles, CA, USA.
Alberto FerlinDepartment of Medicine, University of Padova, Padua, Italy.
Marija GamulinDepartment of Oncology, University Hospital Center Zagreb, University of Zagreb School of Medicine, Zagreb, Croatia.
Jourik A GietemaDepartment of Medical Oncology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
Anna Gonzalez-NieraHuman Genotyping Core Unit, Spanish National Cancer Centre (CNIO), Madrid, Spain.
Tom GrotmolCancer Registry of Norway, Oslo Metropolitan University, Oslo, Norway.
Robert J HamiltonRadboud University Medical Center, Nijmegen, the Netherlands.
Mark HarlandDepartment of Surgery (Urology), University of Toronto and The Princess Margaret Cancer Centre, Toronto, ON, Canada.
Trine B HaugenDepartment of Life Sciences and Health, Oslo Metropolitan University, Oslo, Norway.
Russ HauserDepartment of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Michelle A T HildebrandtDepartment of Lymphoma and Myeloma, University of Texas, MD Anderson Cancer Center, Houston, TX, USA.
Robert KarlssonDepartment of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden.
Lambertus A KiemeneyRadboud University Medical Center, Nijmegen, the Netherlands.
Jung KimDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
Davor LesselInstitute of Human Genetics, University of Regensburg, Regensburg, Germany; Institute of Clinical Human Genetics, University Hospital Regensburg, Regensburg, Germany.
Ragnhild A LotheDepartment of Molecular Oncology, Institute for Cancer Research, Oslo University Hospital-Radiumhospitalet, Oslo, Norway.
Chey LovedayDivision of Genetics & Epidemiology, The Institute of Cancer Research, London, UK; William Harvey Research Institute, Queen Mary University, London, UK.
Stephen J ChanockDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
Katherine A McGlynnDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
Coby MeijerDepartment of Medical Oncology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
Kevin T NeadDepartment of Lymphoma and Myeloma, University of Texas, MD Anderson Cancer Center, Houston, TX, USA.
Jeremie NsengimanaBiostatistics Research Group, Population Health Sciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle, UK.
Maja PopovicCancer Epidemiology Unit, Department of Medical Sciences, University of Turin and CPO-Piemonte, Turin, Italy.
Thorunn RafnardeCODE Genetics/Amgen, Reykjavik, Iceland.
Lorenzo RichiardiCancer Epidemiology Unit, Department of Medical Sciences, University of Turin and CPO-Piemonte, Turin, Italy.
Maria S RoccaDepartment of Medicine, University of Padova, Padua, Italy.
Stephen M SchwartzEpidemiology Program, Fred Hutchinson Cancer Center, Seattle, WA, USA; Department of Epidemiology, University of Washington, Seattle, WA, USA.
Rolf I SkotheimDepartment of Molecular Oncology, Institute for Cancer Research, Oslo University Hospital-Radiumhospitalet, Oslo, Norway.
Kari StefanssondeCODE Genetics/Amgen, Reykjavik, Iceland.
Douglas R StewartDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
Clare TurnbullDivision of Genetics & Epidemiology, The Institute of Cancer Research, London, UK.
David J VaughnDivision of Hematology/Oncology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Sofia B WingeDepartment of Growth and Reproduction, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark.
Tongzhang ZhengDepartment of Epidemiology, Brown School of Public Health, Brown University, Providence, RI, USA.
Alvaro N MonteiroDepartment of Cancer Epidemiology, Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
Kristian AlmstrupDepartment of Growth and Reproduction, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark; Department of Cellular and Molecular Medicine, University of Copenhagen, Copenhagen, Denmark.
Peter A KanetskyDepartment of Cancer Epidemiology, Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
Katherine L NathansonDivision of Translational Medicine and Human Genetics, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Fredrik WiklundDepartment of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden. Electronic address: fredrik.wiklund@ki.se.
Testicular Cancer Consortium

Funding

Translational Research Support CoreP30ES013508 · NIEHS · UNIVERSITY OF PENNSYLVANIA · PI A. Clementina Mesaros · 2006 to 2026
$35.3M
Post GWA Studies in Testicular Germ Cell TumorsU01CA164947 · NCI · UNIVERSITY OF PENNSYLVANIA · PI KANETSKY, PETER A, NATHANSON, KATHERINE L. · 2012 to 2024
$11.7M
NCI NIH HHS U01 CA164947NIEHS NIH HHS P30 ES013508
6 · The paper itself

Abstract

Transcriptome-wide association studies (TWASs) have the potential to identify susceptibility genes associated with testicular germ cell tumors (TGCTs). We conducted a comprehensive TGCT TWAS by integrating genome-wide association study (GWAS) summary data with predicted expression models from normal testis, TGCT tissues, and a cross-tissue panel that encompasses shared regulatory features across 22 normal tissues, including the testis. Gene associations were evaluated while accounting for variant-level effects from GWASs, followed by fine-mapping analyses in regions exhibiting multiple TWAS signals, and finally supplemented by colocalization analysis. Expression and protein patterns of identified TWAS genes were further examined in relevant tissues. Our analysis tested 19,805 gene-disease links, revealing 165 TGCT-associated genes with a false discovery rate of less than 0.01. We prioritized 46 candidate genes by considering GWAS-inflated signals, correlations between neighboring genes, and evidence of colocalization. Among these, 23 genes overlap with 22 GWAS loci, with 7 being associations not previously implicated in TGCT risk. Additionally, 23 genes located within 21 loci are at least 1 Mb away from published GWAS index variants. The 46 prioritized genes display expression levels consistent with expected expression levels in human gonadal cell types and precursor tumor cells and significant enrichment in TGCTs. Additionally, immunohistochemistry revealed protein-level accumulation of two candidate genes, ARID3B and GINM1, in both precursor and tumor cells. These findings enhance our understanding of the genetic predisposition to TGCTs and underscore the importance of further functional investigations into these candidate genes.

Indexed as

Genetic Predisposition to DiseaseGenome-Wide Association StudyNeoplasms, Germ Cell and EmbryonalTesticular NeoplasmsTranscriptomeGene Expression ProfilingGene Expression Regulation, NeoplasticHumansMalePolymorphism, Single Nucleotidecolocalization analysistesticular germ cell tumorstranscriptome-wide association study

Identifiers

PMID39999848
PMCPMC11947167

What OpenQuestion 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 OpenQuestion graph.