ArticleJournal of the National Cancer Institute2020
A Transcriptome-Wide Association Study Identifies Novel Candidate Susceptibility Genes for Pancreatic Cancer.
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59 citing papers in PubMed, 1 synthesis or guideline pooled it, 89 citations in OpenAlex.
- Integrative transcriptome-wide analysis of atopic dermatitis for drug repositioning.Communications biology · 2022Pooled it
- Mapping Genetic Regulation of Transcription to Identify Functional Variants and Genes Associated with Pancreatic Cancer Risk.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Novel Genetic Risk Loci for Pancreatic Ductal Adenocarcinoma Identified in a Genome-wide Study of African Ancestry Individuals.medRxiv : the preprint server for health sciences · 2026Article
- Characterization of a pancreatic cancer GWAS signal suggests PDX1 buffers stress in the exocrine pancreas.medRxiv : the preprint server for health sciences · 2026Article
- Integrative screening identifies functional variants and VNTRs underlying GWAS signals at the 5p15.33 multi-cancer susceptibility locus.medRxiv : the preprint server for health sciences · 2026Article
- Large-scale integration of omics and electronic health records to identify potential risk protein biomarkers and therapeutic drugs for cancer prevention.American journal of human genetics · 2026Article
- Co-expression-wide association studies link genetically regulated interactions with complex traits.Nature communications · 2025Article
- A Transcriptome-Wide Association Study Identifies Candidate Susceptibility Loci and Genes for Lung Cancer Risk.Cancer medicine · 2025Article
- CADET: Enhanced transcriptome-wide association analyses in admixed samples using eQTL summary data.American journal of human genetics · 2025Article
- CLPTM1L interacts with ERLIN2 to stabilize SREBP1 and drive tumorigenesis in nasopharyngeal carcinoma.Cell death & disease · 2025Article
- Allelic effects on KLHL17 expression underlie a pancreatic cancer genome-wide association signal at chr1p36.33.Nature communications · 2025Article
- Unveiling circulating targets in pancreatic cancer: Insights from proteogenomic evidence and clinical cohorts.iScience · 2025Article
- Multiome-wide Association Studies: Novel Approaches for Understanding Diseases.Genomics, proteomics & bioinformatics · 2024Review
- A cross-tissue transcriptome-wide association study identifies WDPCP as a potential susceptibility gene for coronary atherosclerosis.Atherosclerosis plus · 2024Article
- Germline DNA Damage Repair Gene Alterations in Patients with Metachronous Breast and Colorectal Cancer.International journal of molecular sciences · 2024Article
- Allelic effects onmedRxiv : the preprint server for health sciences · 2024Article
- Large-Scale Alternative Polyadenylation-Wide Association Studies to Identify Putative Cancer Susceptibility Genes.Cancer research · 2024Article
- Transcriptome-Wide Association Study Reveals Potentially Candidate Genes Responsible for Milk Production Traits in Buffalo.International journal of molecular sciences · 2024Article
- Regulome-wide association study identifies genetically driven accessible regions associated with pancreatic cancer risk.International journal of cancer · 2024Article
- Large-scale integrative analysis of juvenile idiopathic arthritis for new insight into its pathogenesis.Arthritis research & therapy · 2024Article
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Authors and funding
95 authors at 20 institutions in 14 countries.
Jun ZhongLaboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Ashley JermusykLaboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Lang WuDivision of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, USA.
Jason W HoskinsLaboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Irene CollinsLaboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Evelina MocciDepartment of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD, USA.
Mingfeng ZhangLaboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Lei SongDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Charles C ChungDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Tongwu ZhangDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Wenming XiaoNational Center for Toxicological Research, US Food and Drug Administration, Jefferson, AR, USA.
Demetrius AlbanesDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Gabriella AndreottiDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Alan A ArslanDepartment of Obstetrics and Gynecology, New York University School of Medicine, New York, NY, USA.
Ana BabicDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
William R BamletDepartment of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, MN, USA.
Laura Beane-FreemanDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Sonja BerndtDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Ayelet BorgidaLunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, Ontario, Canada.
Paige M BracciDepartment of Epidemiology and Biostatistics, University of California, CA, USA.
Lauren BraisDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Paul BrennanInternational Agency for Research on Cancer, Lyon, France.
Bas Bueno-de-MesquitaDepartment for Determinants of Chronic Diseases, National Institute for Public Health and the Environment, BA, Bilthoven, The Netherlands.
Julie BuringDivision of Preventive Medicine, Brigham and Women's Hospital, Boston, MA, USA.
Federico CanzianGenomic Epidemiology Group, German Cancer Research Center, Heidelberg, Germany.
Erica J ChildsDepartment of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD, USA.
Michelle CotterchioCancer Care Ontario, University of Toronto, Toronto, Ontario, Canada.
Mengmeng DuDepartment of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Eric J DuellUnit of Nutrition and Cancer, Cancer Epidemiology Research Program, Bellvitge Biomedical Research Institute, Catalan Institute of Oncology, Barcelona, Spain.
Charles FuchsYale Cancer Center, New Haven, CT, USA.
Steven GallingerLunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, Ontario, Canada.
J Michael GazianoDivision of Preventive Medicine, Brigham and Women's Hospital, Boston, MA, USA.
Graham G GilesCancer Epidemiology and Intelligence Division, Cancer Council Victoria, Melbourne, VIC, Australia.
Edward GiovannucciDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Michael GogginsDepartment of Pathology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins School of Medicine, Baltimore, MD, USA.
Gary E GoodmanDivision of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Phyllis J GoodmanSWOG Statistical Center, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Christopher HaimanDepartment of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Patricia HartgeDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Manal HasanDepartment of Epidemiology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Kathy J HelzlsouerDivision of Cancer Control and Population Sciences, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Elizabeth A HollyDepartment of Epidemiology and Biostatistics, University of California, San Francisco, CA, USA.
Eric A KleinGlickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, OH, USA.
Manolis KogevinasISGlobal, Centre for Research in Environmental Epidemiology, Barcelona, Spain.
Robert J KurtzDepartment of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Loic LeMarchandCancer Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI, USA.
Núria MalatsGenetic and Molecular Epidemiology Group, Spanish National Cancer Research Center, Madrid, Spain.
Satu MännistöDepartment of Public Health Solutions, National Institute for Health and Welfare, Helsinki, Finland.
Roger MilneCancer Epidemiology and Intelligence Division, Cancer Council Victoria, Melbourne, VIC, Australia.
Rachel E NealePopulation Health Department, QIMR Berghofer Medical Research Institute, Brisbane, Australia.
Kimmie NgDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Ofure ObazeeGenomic Epidemiology Group, German Cancer Research Center, Heidelberg, Germany.
Ann L ObergDepartment of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, MN, USA.
Irene OrlowDepartment of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Alpa V PatelEpidemiology Research Program, American Cancer Society, Atlanta, GA, USA.
Ulrike PetersDivision of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Miquel PortaCIBER Epidemiología y Salud Pública, Barcelona, Spain.
Nathaniel RothmanDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Ghislaine SceloInternational Agency for Research on Cancer, Lyon, France.
Howard D SessoDivision of Preventive Medicine, Brigham and Women's Hospital, Boston, MA, USA.
Gianluca SeveriCentre de Recherche en Épidémiologie et Santé des Populations (CESP, Inserm U1018), Facultés de Medicine, Université Paris-Saclay, UPS, UVSQ, Gustave Roussy, Villejuif, France.
Sabina SieriEpidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy.
Debra SilvermanDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Malin SundDepartment of Surgical and Perioperative Sciences, Umeå University, Umeå, Sweden.
Anne TjønnelandDanish Cancer Society Research Center, Copenhagen, Denmark.
Mark D ThornquistDivision of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Geoffrey S TobiasDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Antonia Trichopoulou
Stephen K Van Den EedenDivision of Research, Kaiser Permanente Northern California, Oakland, CA, USA.
Kala VisvanathanDepartment of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
Jean Wactawski-WendeDepartment of Epidemiology and Environmental Health, University at Buffalo, Buffalo, NY, USA.
Nicolas WentzensenDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Emily WhiteDivision of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Herbert YuCancer Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI, USA.
Chen YuanDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Anne Zeleniuch-JacquotteDepartment of Population Health, New York University School of Medicine, New York, NY, USA.
Robert HooverDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Kevin BrownLaboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Charles KooperbergDivision of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Harvey A RischDepartment of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, CT, USA.
Eric J JacobsBehavioral and Epidemiology Research Group, American Cancer Society, Atlanta, GA, USA.
Donghui LiDepartment of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Kai YuDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Xiao-Ou ShuDivision of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, USA.
Stephen J ChanockDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Brian M WolpinDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Rachael Z Stolzenberg-SolomonDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Nilanjan ChatterjeeDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Alison P KleinDepartment of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD, USA.
Jill P SmithDepartment of Medicine, Georgetown University, Washington, DC, USA.
Peter KraftDepartment of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Jianxin ShiDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Gloria M PetersenDepartment of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, MN, USA.
Wei ZhengDivision of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, USA.
Laufey T AmundadottirLaboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
National Institutes of Health · USDana-Farber Cancer Institute · USFred Hutch Cancer Center · USJohns Hopkins University · USBrigham and Women's Hospital · USMayo Clinic · USMemorial Sloan Kettering Cancer Center · USThe University of Melbourne · AUVanderbilt University Medical Center · USAmerican Cancer Society · USGerman Cancer Research Center · DEMount Sinai Hospital · CANew York University · USThe University of Texas MD Anderson Cancer Center · USUniversitat Autònoma de Barcelona · ESUniversity of Hawaiʻi at Mānoa · USCentre international de recherche sur le cancer · FRCleveland Clinic · USFinnish Institute for Health and Welfare · FIFondazione IRCCS Istituto Nazionale dei Tumori · IT
Funding
X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI SELWYN M VICKERS · 1985 to 2026
$347.4MSWOG Foreign AccrualsU10CA037429 · NCI · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI BLANKE, CHARLES D., MEYSKENS, FRANK L. · 1985 to 2014
$205.2MSWOG NCORP Research BaseUG1CA189974 · NCI · THE HOPE FOUNDATION · PI CHARLES D. BLANKE, DAWN HERSHMAN · 2014 to 2026
$80.6MTumor Antigens for Individual Signatures and TherapyP50CA062924 · NCI · JOHNS HOPKINS UNIVERSITY · PI THOMPSON, ELIZABETH D · 1993 to 2022
$54.6MData sharing: the Colon Cancer Family Registry CohortU01CA167551 · NCI · UNIVERSITY OF MELBOURNE · PI Daniel David BUCHANAN, Steven Gallinger · 2018 to 2026
$16.8MONTARIO REGISTRY FOR STUDIES OF FAMILIAL COLON CANCERU01CA074783 · NCI · CANCER CARE ONTARIO · PI GALLINGER, STEVEN · 1997 to 2008
$12.5MTranslational Research Enhancement CoreP30DK089502 · NIDDK · JOHNS HOPKINS UNIVERSITY · PI ZACHOS, NICHOLAS CONSTANTINE · 2011 to 2020
$12.0MValidation and Fine-Scale Mapping of Pancreatic Cancer Susceptibility Loci (Study)R01CA154823 · NCI · JOHNS HOPKINS UNIVERSITY · PI KLEIN, ALISON P · 2011 to 2020
$5.7MPCPT and SELECT Cohorts: Core Infrastructure Support for Cancer ResearchU01CA182883 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI TANGEN, CATHERINE M., THOMPSON, IAN M. · 2019 to 2023
$5.4MPCPT and SELECT cohorts: Core Infrastructure Support for Cancer Research UM1CA182883 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI TANGEN, CATHERINE M., THOMPSON, IAN M. · 2013 to 2017
$5.2MShanghai Men's Health StudyUM1CA173640 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI SHU, XIAO-OU · 2013 to 2017
$4.9MThe NYU Women's Health StudyUM1CA182934 · NCI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI ZELENIUCH-JAQUOTTE, ANNE · 2015 to 2019
$3.7MNCI NIH HHS K07 CA222159NCI NIH HHS P30 CA008748NCI NIH HHS P50 CA062924NCI NIH HHS R01 CA154823NCI NIH HHS R01 CA188214NCI NIH HHS U01 CA074783NCI NIH HHS U01 CA167462NCI NIH HHS U01 CA167551NCI NIH HHS U01 CA182883NCI NIH HHS U10 CA037429NCI NIH HHS UG1 CA189974NCI NIH HHS UM1 CA173640NCI NIH HHS UM1 CA182883NCI NIH HHS UM1 CA182934NIDDK NIH HHS P30 DK089502World Health Organization 001
Abstract
backgroundAlthough 20 pancreatic cancer susceptibility loci have been identified through genome-wide association studies in individuals of European ancestry, much of its heritability remains unexplained and the genes responsible largely unknown.
methodsTo discover novel pancreatic cancer risk loci and possible causal genes, we performed a pancreatic cancer transcriptome-wide association study in Europeans using three approaches: FUSION, MetaXcan, and Summary-MulTiXcan. We integrated genome-wide association studies summary statistics from 9040 pancreatic cancer cases and 12 496 controls, with gene expression prediction models built using transcriptome data from histologically normal pancreatic tissue samples (NCI Laboratory of Translational Genomics [n = 95] and Genotype-Tissue Expression v7 [n = 174] datasets) and data from 48 different tissues (Genotype-Tissue Expression v7, n = 74-421 samples).
resultsWe identified 25 genes whose genetically predicted expression was statistically significantly associated with pancreatic cancer risk (false discovery rate < .05), including 14 candidate genes at 11 novel loci (1p36.12: CELA3B; 9q31.1: SMC2, SMC2-AS1; 10q23.31: RP11-80H5.9; 12q13.13: SMUG1; 14q32.33: BTBD6; 15q23: HEXA; 15q26.1: RCCD1; 17q12: PNMT, CDK12, PGAP3; 17q22: SUPT4H1; 18q11.22: RP11-888D10.3; and 19p13.11: PGPEP1) and 11 at six known risk loci (5p15.33: TERT, CLPTM1L, ZDHHC11B; 7p14.1: INHBA; 9q34.2: ABO; 13q12.2: PDX1; 13q22.1: KLF5; and 16q23.1: WDR59, CFDP1, BCAR1, TMEM170A). The association for 12 of these genes (CELA3B, SMC2, and PNMT at novel risk loci and TERT, CLPTM1L, INHBA, ABO, PDX1, KLF5, WDR59, CFDP1, and BCAR1 at known loci) remained statistically significant after Bonferroni correction.
conclusionsBy integrating gene expression and genotype data, we identified novel pancreatic cancer risk loci and candidate functional genes that warrant further investigation.
Indexed as
Databases, GeneticGene ExpressionGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansPancreatic NeoplasmsPolymorphism, Single NucleotideQuantitative Trait LociTranscriptome
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