Evidence map›Paper›PMID 34317694›Full record

ArticleHGG advances2021

Pleiotropy-guided transcriptome imputation from normal and tumor tissues identifies candidate susceptibility genes for breast and ovarian cancer.

Siddhartha P Kar, Daniel P C Considine, Jonathan P Tyrer, Jasmine T Plummer, Stephanie Chen, Felipe S Dezem, Alvaro N Barbeira, Padma S Rajagopal, Will T Rosenow, Fernando Moreno and 48 more

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

Article in HGG advances, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed, 2 pooled it
2.6field-weighted citation impact, top 10% 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

16 citing papers in PubMed, 2 syntheses or guidelines pooled it, 17 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
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  10. bioRxiv : the preprint server for biology · 2023
    Article
  11. Article
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  13. Molecular Management of High-Grade Serous Ovarian Carcinoma.International journal of molecular sciences · 2022
    Review
  14. Article
  15. Article
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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

58 authors at 20 institutions in 14 countries.

Siddhartha P Kar *Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, UK.
Daniel P C Considine *Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
Jonathan P TyrerCentre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK.
Jasmine T PlummerCenter for Bioinformatics and Functional Genomics, Department of Biomedical Science, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Stephanie ChenCenter for Bioinformatics and Functional Genomics, Department of Biomedical Science, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Felipe S DezemCenter for Bioinformatics and Functional Genomics, Department of Biomedical Science, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Alvaro N BarbeiraSection of Genetic Medicine, Department of Medicine, University of Chicago, Chicago, IL, USA.
Padma S RajagopalSection of Hematology/Oncology, Department of Medicine, University of Chicago, Chicago, IL, USA.
Will T RosenowCenter for Public Health Genomics, University of Virginia, Charlottesville, VA, USA.
Fernando MorenoDepartment of Oncology, Hospital Clínico San Carlos, Madrid, Spain.
Clara BodelonDivison of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
Jenny Chang-ClaudeDivision of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Georgia Chenevix-TrenchDepartment of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.
Anna deFazioCentre for Cancer Research, The Westmead Institute for Medical Research, The University of Sydney, Sydney, NSW, Australia.
Thilo DörkGynaecology Research Unit, Hannover Medical School, Hannover, Germany.
Arif B EkiciInstitute of Human Genetics, University Hospital Erlangen, Erlangen, Germany.
Ailith EwingMRC Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, UK.
George FountzilasLaboratory of Molecular Oncology, Hellenic Foundation for Cancer Research, Aristotle University of Thessaloniki School of Medicine, Thessaloniki, Greece.
Ellen L GoodeDepartment of Quantitative Health Sciences, Division of Epidemiology, Mayo Clinic, Rochester, MN, USA.
Mikael HartmanDepartment of Surgery, Yong Loo Lin School of Medicine, National University of Singapore and National University Health System, Singapore, Singapore.
Florian HeitzDepartment of Gynecology and Gynecologic Oncology, Kliniken Essen-Mitte/Evang., Essen, Germany.
Peter HillemannsDepartment of Gynecology and Obstetrics, Hannover Medical School, Hannover, Germany.
Estrid HøgdallDepartment of Virus, Lifestyle, and Genes, Danish Cancer Society Research Center, Copenhagen, Denmark.
Claus K HøgdallThe Juliane Marie Centre, Department of Gynecology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
Tomasz HuzarskiDepartment of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University, Szczecin, Poland.
Allan JensenDepartment of Lifestyle, Reproduction, and Cancer, Danish Cancer Society Research Center, Copenhagen, Denmark.
Beth Y KarlanDavid Geffen School of Medicine, Department of Obstetrics and Gynecology, University of California at Los Angeles, Los Angeles, CA, USA.
Elza KhusnutdinovaInstitute of Biochemistry and Genetics, Ufa Federal Research Centre of the Russian Academy of Sciences, Ufa, Russia.
Lambertus A KiemeneyRadboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, the Netherlands.
Susanne K KjaerDepartment of Virus, Lifestyle, and Genes, Danish Cancer Society Research Center, Copenhagen, Denmark.
Rüdiger KlapdorDepartment of Gynecology and Obstetrics, Hannover Medical School, Hannover, Germany.
Martin KöbelDepartment of Pathology and Laboratory Medicine, University of Calgary, Foothills Medical Center, Calgary, AB, Canada.
Jingmei LiDepartment of Surgery, Yong Loo Lin School of Medicine, National University of Singapore and National University Health System, Singapore, Singapore.
Clemens LiebrichDepartment of Obstetrics and Gynecology, Klinikum Wolfsburg, Wolfsburg, Germany.
Taymaa MayDivision of Gynecologic Oncology, University Health Network, Princess Margaret Hospital, Toronto, ON, Canada.
Håkan OlssonDivision of Oncology, Department of Clinical Sciences, Lund University, Lund, Sweden.
Jennifer B PermuthDepartments of Cancer Epidemiology and Gastrointestinal Oncology, Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
Paolo PeterlongoGenome Diagnostics Program, IFOM-The FIRC Institute of Molecular Oncology, Milan, Italy.
Paolo RadiceUnit of Molecular Bases of Genetic Risk and Genetic Testing, Department of Research, Fondazione IRCCS Istituto Nazionale dei Tumori (INT), Milan, Italy.
Susan J RamusSchool of Women's and Children's Health, Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia.
Marjorie J RigganDepartment of Obstetrics and Gynecology, Duke University Medical Center, Durham, NC, USA.
Harvey A RischDepartment of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, CT, USA.
Emmanouil SaloustrosDepartment of Oncology, University Hospital of Larissa, Larissa, Greece.
Jacques SimardGenomics Center, Centre Hospitalier Universitaire de Québec - Université Laval Research Center, Québec City, QC, Canada.
Lukasz M SzafronMaria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland.
Linda TitusMuskie School of Public Service, University of Southern Maine, Portland, ME, USA.
Cheryl L ThompsonDepartment of Nutrition, Case Western Reserve University, Cleveland, OH, USA.
Robert A VierkantDepartment of Quantitative Health Sciences, Division of Clinical Trials and Biostatistics, Mayo Clinic, Rochester, MN, USA.
Stacey J WinhamDepartment of Quantitative Health Sciences, Division of Computational Biology, Mayo Clinic, Rochester, MN, USA.
Wei ZhengDivision of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN, USA.
Jennifer A DohertyHuntsman Cancer Institute, Department of Population Health Sciences, University of Utah, Salt Lake City, UT, USA.
Andrew BerchuckDivision of Gynecologic Oncology, Department of Obstetrics and Gynecology, Duke University Medical Center, Durham, NC, USA.
Kate LawrensonCenter for Bioinformatics and Functional Genomics, Department of Biomedical Science, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Hae Kyung ImSection of Genetic Medicine, Department of Medicine, University of Chicago, Chicago, IL, USA.
Ani W ManichaikulCenter for Public Health Genomics, University of Virginia, Charlottesville, VA, USA.
Paul D P PharoahCentre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
Simon A GaytherCenter for Bioinformatics and Functional Genomics, Department of Biomedical Science, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Joellen M SchildkrautDepartment of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA, USA.
Cedars-Sinai Medical Center · USMayo Clinic in Florida · USMedizinische Hochschule Hannover · DEUniversity of Chicago · USDanish Cancer Society · DKDuke Medical Center · USUniversity of Cambridge · GBUniversity of Virginia · USAristotle University of Thessaloniki · GRBashkir State University · RUCancer Research UK Cambridge Center · GBCase Western Reserve University · USCentre hospitalier universitaire de Québec · CACharité - Universitätsmedizin Berlin · DEEmory University · USFondazione IRCCS Istituto Nazionale dei Tumori · ITFoothills Medical Centre · CAFraunhofer Project Centre Wolfsburg · DEHerlev Hospital · DKHospital Clínico San Carlos · ES

Funding

Use of microfluidic tumor cultures to enable clinical trials of therapies for ovarian cancerP50CA136393 · NCI · MAYO CLINIC ROCHESTER · PI ELLEN L. GOODE · 2009 to 2026
$37.0M
Pilot and Feasibility ProgramP30DK020595 · NIDDK · UNIVERSITY OF CHICAGO · PI Raghavendra G Mirmira · 2013 to 2026
$20.9M
Epidemiologic StudiesU19CA148065 · NCI · HARVARD SCHOOL OF PUBLIC HEALTH · PI AHSAN, HABIBUL, BRUGGE, JOAN SIEFERT · 2010 to 2014
$10.6M
Ovarian cancer GWAS discovery, expansion and replication (N2 - Project #1)U19CA148112 · NCI · H. LEE MOFFITT CANCER CTR & RES INST · PI SELLERS, THOMAS A · 2010 to 2014
$10.2M
Relating Molecular Subgroups of Endometriosis-Associated Ovarian Cancers to Survival and RiskR01CA248288 · NCI · MAYO CLINIC ROCHESTER · PI Stacey J Winham · 2021 to 2026
$4.8M
COLLABORATIVE STUDY OF OVARIAN CANCER IN TWO RISK GROUPSR01CA058598 · NCI · UNIVERSITY OF HAWAII AT MANOA · PI GOODMAN, MARC T · 1993 to 2012
$4.6M
Genomic and Transcriptomic Analysis of Breast and Ovarian CancersR01CA211574 · NCI · UNIVERSITY OF VIRGINIA · PI GAYTHER, SIMON ANDREW, SCHILDKRAUT, JOELLEN M. · 2018 to 2022
$3.1M
The Mitochondrial Genome and Ovarian Cancer RiskR01CA149429 · NCI · H. LEE MOFFITT CANCER CTR & RES INST · PI PHELAN, CATHERINE · 2010 to 2015
$3.1M
Common biology underlying pleiotropic breast, prostate and ovarian cancer risk lociR01CA259058 · NCI · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI MATTHEW L FREEDMAN, Simon Andrew Gayther · 2022 to 2026
$2.5M
Cancer Research UK 16561Cancer Research UK 16563NCI NIH HHS P50 CA136393NCI NIH HHS R01 CA058598NCI NIH HHS R01 CA149429NCI NIH HHS R01 CA211574NCI NIH HHS R01 CA248288NCI NIH HHS R01 CA259058NCI NIH HHS U19 CA148065NCI NIH HHS U19 CA148112NIDDK NIH HHS P30 DK020595
6 · The paper itself

Abstract

Familial, sequencing, and genome-wide association studies (GWASs) and genetic correlation analyses have progressively unraveled the shared or pleiotropic germline genetics of breast and ovarian cancer. In this study, we aimed to leverage this shared germline genetics to improve the power of transcriptome-wide association studies (TWASs) to identify candidate breast cancer and ovarian cancer susceptibility genes. We built gene expression prediction models using the PrediXcan method in 681 breast and 295 ovarian tumors from The Cancer Genome Atlas and 211 breast and 99 ovarian normal tissue samples from the Genotype-Tissue Expression project and integrated these with GWAS meta-analysis data from the Breast Cancer Association Consortium (122,977 cases/105,974 controls) and the Ovarian Cancer Association Consortium (22,406 cases/40,941 controls). The integration was achieved through application of a pleiotropy-guided conditional/conjunction false discovery rate (FDR) approach in the setting of a TWASs. This identified 14 candidate breast cancer susceptibility genes spanning 11 genomic regions and 8 candidate ovarian cancer susceptibility genes spanning 5 genomic regions at conjunction FDR < 0.05 that were >1 Mb away from known breast and/or ovarian cancer susceptibility loci. We also identified 38 candidate breast cancer susceptibility genes and 17 candidate ovarian cancer susceptibility genes at conjunction FDR < 0.05 at known breast and/or ovarian susceptibility loci. The 22 genes identified by our cross-cancer analysis represent promising candidates that further elucidate the role of the transcriptome in mediating germline breast and ovarian cancer risk.

Identifiers

PMID34317694
PMCPMC8312632
OpenAlexW3167899697

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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.