ArticleNature medicine2024
Selection, optimization and validation of ten chronic disease polygenic risk scores for clinical implementation in diverse US populations.
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Article in Nature medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 159 papers, 3 of them syntheses that pooled it.
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159citing papers in PubMed, 3 pooled it
96.3field-weighted citation impact, top 1% of its field
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Who cites it
159 citing papers in PubMed, 3 syntheses or guidelines pooled it, 177 citations in OpenAlex.
- Multi-ancestry polygenic risk scores for the prediction of type 2 diabetes and complications in diverse ancestries.The lancet. Diabetes & endocrinology · 2026Pooled it
- Genome-wide meta-analyses of cross substance use disorders in diverse populations.Molecular psychiatry · 2026Pooled it
- Human genetic diversity across South Asian populations: A systematic review and meta-analysis.Medicine · 2025Pooled it
- Development and pilot testing of a prostate cancer polygenic risk report.BMC medical genomics · 2026Trial
- Integrating breast cancer polygenic risk scores at scale in the WISDOM Study: a national randomized personalized screening trial.Genome medicine · 2025Trial
- All of Us diversity and scale yield context-dependent improvements in polygenic prediction.Nature genetics · 2026Article
- SPLENDID incorporates continuous genetic ancestry in biobank-scale data to improve polygenic risk prediction across diverse populations.Nature methods · 2026Article
- Recommendations for return of secondary genomic findings in observational cohort studies.Nature genetics · 2026Review
- Polygenic risk scores in human genetics for study design discovery and translation.Human genetics · 2026Review
- Insights into the Complexities of Pharmacotherapy Parameters in Artificial Intelligence Models for Drug Selection, Precision Personalised Medicine and Optimal Therapeutic Outcomes.Pharmaceutics · 2026Review
- Development and Validation of a Clinical Polygenic Risk Report in U.S.-Based Health Systems for 8 Cardiovascular Conditions.Journal of the American College of Cardiology · 2026Article
- Cross-ancestry and cross-disorder transferability of polygenic risk scores for obsessive-compulsive disorder.Translational psychiatry · 2026Article
- From polygenic risk to functional genomics: a framework for precision gynecological disease modeling.Nature communications · 2026Review
- Large-scale admixture mapping in the All of Us Research Program improves the characterization of cross-population phenotypic differences.Nature communications · 2026Article
- Pervasive interactions between exposures and polygenic risk can inform more effective clinical and behavioral interventions.Nature genetics · 2026Article
- The role of polygenic risk in Alzheimer's disease prediction for African Americans.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Observational
- Performance of Polygenic Risk Scores for Atherosclerotic Cardiovascular Disease in theCirculation. Genomic and precision medicine · 2026Article
- Exploring the use of machine and deep learning in genome-wide association studies: a comprehensive review.BioData mining · 2026Review
- ProLM: a plasma proteomics pretrained model for the general population.Nature communications · 2026Article
- A mixed-methods exploration of stakeholder experiences and perspectives on integrating polygenic breast cancer risk scores into Swedish clinical practice.BMC health services research · 2026Article
99 more citing papers are in PubMed but not listed here.
Corrections and comments
- Update of
Authors and funding
79 authors at 16 institutions in 3 countries.
Niall J Lennon *Broad Institute of MIT and Harvard, Cambridge, MA, USA. nlennon@broadinstitute.org.ORCID 0000-0002-2874-7371
Leah C Kottyan *Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, OH, USA.
Christopher KachulisBroad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID 0000-0003-2095-7419
Noura S Abul-HusnIcahn School of Medicine at Mount Sinai, New York, NY, USA.ORCID 0000-0002-5179-1944
Josh AriasNational Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.ORCID 0000-0001-6545-6656
Gillian BelbinIcahn School of Medicine at Mount Sinai, New York, NY, USA.
Jennifer E BelowVanderbilt University Medical Center, Nashville, TN, USA.ORCID 0000-0002-1346-1872
Sonja I BerndtNational Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
Wendy K ChungColumbia University, New York, NY, USA.ORCID 0000-0003-3438-5685
James J CiminoUniversity of Alabama at Birmingham, Birmingham, AL, USA.ORCID 0000-0003-4101-1622
Ellen Wright ClaytonVanderbilt University Medical Center, Nashville, TN, USA.ORCID 0000-0002-0308-4110
John J ConnollyChildren's Hospital of Philadelphia, Philadelphia, PA, USA.
David R CrosslinTulane University, New Orleans, LA, USA.
Ozan DikilitasMayo Clinic, Rochester, MI, USA.ORCID 0000-0002-9906-8608
Digna R Velez EdwardsVanderbilt University Medical Center, Nashville, TN, USA.
QiPing FengVanderbilt University Medical Center, Nashville, TN, USA.ORCID 0000-0002-6213-793X
Marissa FisherBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Robert R FreimuthMayo Clinic, Rochester, MI, USA.
Tian GeMass General Brigham, Boston, MA, USA.
GIANT Consortium
All of Us Research Program
Joseph T GlessnerChildren's Hospital of Philadelphia, Philadelphia, PA, USA.ORCID 0000-0001-5131-2811
Adam S GordonNorthwestern University, Evanston, IL, USA.ORCID 0000-0002-2058-7289
Candace PattersonBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Hakon HakonarsonChildren's Hospital of Philadelphia, Philadelphia, PA, USA.ORCID 0000-0003-2814-7461
Maegan HardenBroad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID 0000-0002-3607-6416
Margaret HarrChildren's Hospital of Philadelphia, Philadelphia, PA, USA.
Joel N HirschhornBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Clive HoggartIcahn School of Medicine at Mount Sinai, New York, NY, USA.
Li HsuFred Hutchinson Cancer Center, Seattle, WA, USA.ORCID 0000-0001-8168-4712
Marguerite R IrvinUniversity of Alabama at Birmingham, Birmingham, AL, USA.
Gail P JarvikUniversity of Washington, Seattle, WA, USA.
Elizabeth W KarlsonMass General Brigham, Boston, MA, USA.
Atlas KhanColumbia University, New York, NY, USA.ORCID 0000-0002-6651-2725
Amit KheraBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Krzysztof KirylukColumbia University, New York, NY, USA.ORCID 0000-0002-5047-6715
Iftikhar KulloMayo Clinic, Rochester, MI, USA.ORCID 0000-0002-6524-3471
Katie LarkinBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Nita LimdiUniversity of Alabama at Birmingham, Birmingham, AL, USA.
Jodell E LinderVanderbilt University Medical Center, Nashville, TN, USA.ORCID 0000-0002-0081-4712
Ruth J F LoosNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Yuan LuoNorthwestern University, Evanston, IL, USA.ORCID 0000-0003-0195-7456
Edyta MalolepszaBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Teri A ManolioNational Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.ORCID 0000-0001-5844-4382
Lisa J MartinCincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, OH, USA.ORCID 0000-0001-8702-9946
Li McCarthyBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Elizabeth M McNallyNorthwestern University, Evanston, IL, USA.
James B MeigsMass General Brigham, Boston, MA, USA.
Tesfaye B MershaCincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, OH, USA.ORCID 0000-0002-9189-8447
Jonathan D MosleyVanderbilt University Medical Center, Nashville, TN, USA.ORCID 0000-0001-6421-2887
Anjene MusickNational Institutes of Health, Bethesda, MD, USA.ORCID 0000-0001-7770-299X
Bahram NamjouCincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, OH, USA.ORCID 0000-0003-4452-7878
Nihal PaiBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Lorenzo L PesceNorthwestern University, Evanston, IL, USA.
Ulrike PetersFred Hutchinson Cancer Center, Seattle, WA, USA.
Josh F PetersonVanderbilt University Medical Center, Nashville, TN, USA.
Cynthia A ProwsCincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, OH, USA.
Megan J PuckelwartzNorthwestern University, Evanston, IL, USA.
Heidi L RehmBroad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID 0000-0002-6025-0015
Dan M RodenVanderbilt University Medical Center, Nashville, TN, USA.ORCID 0000-0002-6302-0389
Elisabeth A RosenthalUniversity of Washington, Seattle, WA, USA.ORCID 0000-0001-6042-4487
Robb RowleyNational Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
Konrad Teodor SawickiNorthwestern University, Evanston, IL, USA.
Daniel J SchaidMayo Clinic, Rochester, MI, USA.
Roelof A J SmitIcahn School of Medicine at Mount Sinai, New York, NY, USA.
Johanna L SmithMayo Clinic, Rochester, MI, USA.ORCID 0000-0002-5861-0413
Jordan W SmollerMass General Brigham, Boston, MA, USA.ORCID 0000-0002-0381-6334
Minta ThomasFred Hutchinson Cancer Center, Seattle, WA, USA.
Hemant TiwariUniversity of Alabama at Birmingham, Birmingham, AL, USA.
Diana M ToledoBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Nataraja Sarma VaitinadinVanderbilt University Medical Center, Nashville, TN, USA.
David VeenstraUniversity of Washington, Seattle, WA, USA.
Theresa L WalunasNorthwestern University, Evanston, IL, USA.ORCID 0000-0002-7653-3650
Zhe WangIcahn School of Medicine at Mount Sinai, New York, NY, USA.ORCID 0000-0002-8046-4969
Wei-Qi WeiVanderbilt University Medical Center, Nashville, TN, USA.ORCID 0000-0003-4985-056X
Chunhua WengColumbia University, New York, NY, USA.
Georgia L WiesnerVanderbilt University Medical Center, Nashville, TN, USA.
Xianyong YinNanjing Medical University, Nanjing, China.ORCID 0000-0001-6454-2384
Eimear E KennyIcahn School of Medicine at Mount Sinai, New York, NY, USA.
Broad Institute · USVanderbilt University Medical Center · USNorthwestern University · USIcahn School of Medicine at Mount Sinai · USNational Institutes of Health · USCincinnati Children's Hospital Medical Center · USMayo Clinic · USChildren's Hospital of Philadelphia · USColumbia University · USMass General Brigham · USUniversity of Alabama at Birmingham · USFred Hutch Cancer Center · USUniversity of Washington · USUniversity of Copenhagen · DKNanjing Medical University · CNTulane University · US
Funding
All of Us Research Program Data and Research CenterOT2OD035404 · OD · VANDERBILT UNIVERSITY MEDICAL CENTER · PI Melissa Basford, DAVID GLAZER · 2023 to 2026
$210.4MTechnology to Empower Changes in Health (TECH) Network Participant Technologies CenterU24OD023176 · OD · SCRIPPS RESEARCH INSTITUTE, THE · PI TOPOL, ERIC JEFFREY · 2016 to 2022
$204.7MPTSC 2.0OT2OD030043 · OD · VIGNET, INC. · PI BEGALE, MARK, JAIN, NEETA · 2020 to 2025
$191.1MPrecision Medicine Initiative Cohort Program BiobankU24OD023121 · OD · MAYO CLINIC ROCHESTER · PI CEKANOVA, MARIA, CICEK, MINE · 2016 to 2024
$185.5MUniversity of Arizona-Banner Health All of Us Research Program OT2OD026549 · OD · UNIVERSITY OF ARIZONA · PI MORENO, FRANCISCO A, REIMAN, ERIC MICHAEL · 2018 to 2023
$78.9MCalifornia Precision Medicine Research Program ConsortiumOT2OD026552 · OD · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI ANTON-CULVER, HODA A, OHNO-MACHADO, LUCILA · 2018 to 2023
$73.4MAll of Us PennsylvaniaOT2OD026554 · OD · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI REIS, STEVEN E, VISWESWARAN, SHYAM · 2018 to 2023
$72.1MNew York City Consortium for Precision MedicineOT2OD026556 · OD · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI BIER, LOUISE E, GHARAVI, ALI G · 2018 to 2023
$67.3MSouthEast Enrollment Center (SEEC) OT2OD026551 · OD · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI CARRASQUILLO, OLVEEN, COLON, VIVIAN · 2018 to 2023
$62.8MSouthern All of Us NetworkOT2OD026548 · OD · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI FOUAD, MONA N., KORF, BRUCE R · 2018 to 2023
$60.5MIllinois Precision Medicine Consortium OT2OD026557 · OD · NORTHWESTERN UNIVERSITY AT CHICAGO · PI AHSAN, HABIBUL, ARGOS, MARIA · 2018 to 2023
$60.5MTrans-America Consortium of the Health Care Systems Research Network for the All of Us Research ProgramOT2OD026550 · OD · HENRY FORD HEALTH SYSTEM · PI AHMEDANI, BRIAN KENNETH, JOHNSON, CHRISTINE C · 2018 to 2022
$57.3MNHGRI NIH HHS U01 HG006379NHGRI NIH HHS U01 HG008657NHGRI NIH HHS U01 HG008680NHGRI NIH HHS U01 HG008685NHGRI NIH HHS U01 HG011166NHGRI NIH HHS U01 HG011167NHGRI NIH HHS U01 HG011169NHGRI NIH HHS U01 HG011172NHGRI NIH HHS U01 HG011175NHGRI NIH HHS U01 HG011176NHGRI NIH HHS U01 HG011181NHLBI NIH HHS R01 HL163854NHLBI NIH HHS R01 HL171809NIAMS NIH HHS P30 AR070549NICHD NIH HHS P50 HD105351NIH HHS OT2 OD025276NIH HHS OT2 OD025277NIH HHS OT2 OD025315NIH HHS OT2 OD025337NIH HHS OT2 OD026548NIH HHS OT2 OD026549NIH HHS OT2 OD026550NIH HHS OT2 OD026551NIH HHS OT2 OD026552NIH HHS OT2 OD026554NIH HHS OT2 OD026555NIH HHS OT2 OD026556NIH HHS OT2 OD026557NIH HHS OT2 OD030043NIH HHS OT2 OD035404NIH HHS U24 OD023121NIH HHS U24 OD023176
Abstract
Polygenic risk scores (PRSs) have improved in predictive performance, but several challenges remain to be addressed before PRSs can be implemented in the clinic, including reduced predictive performance of PRSs in diverse populations, and the interpretation and communication of genetic results to both providers and patients. To address these challenges, the National Human Genome Research Institute-funded Electronic Medical Records and Genomics (eMERGE) Network has developed a framework and pipeline for return of a PRS-based genome-informed risk assessment to 25,000 diverse adults and children as part of a clinical study. From an initial list of 23 conditions, ten were selected for implementation based on PRS performance, medical actionability and potential clinical utility, including cardiometabolic diseases and cancer. Standardized metrics were considered in the selection process, with additional consideration given to strength of evidence in African and Hispanic populations. We then developed a pipeline for clinical PRS implementation (score transfer to a clinical laboratory, validation and verification of score performance), and used genetic ancestry to calibrate PRS mean and variance, utilizing genetically diverse data from 13,475 participants of the All of Us Research Program cohort to train and test model parameters. Finally, we created a framework for regulatory compliance and developed a PRS clinical report for return to providers and for inclusion in an additional genome-informed risk assessment. The initial experience from eMERGE can inform the approach needed to implement PRS-based testing in diverse clinical settings.
Indexed as
Chronic DiseaseGenetic Risk ScorePopulation HealthAdultChildCommunicationGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansRisk FactorsUnited States
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