Evidence map›Paper›PMID 35765100›Full record

ArticleGenome medicine2022

Development and validation of a trans-ancestry polygenic risk score for type 2 diabetes in diverse populations.

Tian Ge, Marguerite R Irvin, Amit Patki, Vinodh Srinivasasainagendra, Yen-Feng Lin, Hemant K Tiwari, Nicole D Armstrong, Barbara Benoit, Chia-Yen Chen, Karmel W Choi and 38 more

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

Article in Genome medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 129 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
129citing papers in PubMed, 4 pooled it
30.3field-weighted citation impact, top 1% 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

129 citing papers in PubMed, 4 syntheses or guidelines pooled it, 165 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Pooled it
  5. Primary care physician use of patient race and polygenic risk scores in medical decision-making.Genetics in medicine : official journal of the American College of Medical Genetics · 2023
    Trial
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Cross-ancestry polygenic risk scores enhance Alzheimer's disease risk prediction in multiethnic cohorts.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
    Article
  15. Article
  16. Article
  17. Article
  18. An integrated cardiometabolic genetic testing program in a predominantly Hispanic population within a community setting.Genetics in medicine : official journal of the American College of Medical Genetics · 2026
    Article
  19. Non-Parametric Ancestry Adjustment for Polygenic Scores.medRxiv : the preprint server for health sciences · 2026
    Article
  20. Article

69 more citing papers are in PubMed but not listed here.

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

48 authors at 19 institutions in 2 countries.

Tian GeCenter for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA. tge1@mgh.harvard.edu.ORCID 0000-0003-4785-4444
Marguerite R IrvinDepartment of Epidemiology, School of Public Health, University of Alabama at Birmingham, Birmingham, AL, USA.
Amit PatkiDepartment of Biostatistics, School of Public Health, University of Alabama at Birmingham, Birmingham, AL, USA.
Vinodh SrinivasasainagendraDepartment of Biostatistics, School of Public Health, University of Alabama at Birmingham, Birmingham, AL, USA.
Yen-Feng LinCenter for Neuropsychiatric Research, National Health Research Institutes, Miaoli, Taiwan.
Hemant K TiwariDepartment of Biostatistics, School of Public Health, University of Alabama at Birmingham, Birmingham, AL, USA.
Nicole D ArmstrongDepartment of Epidemiology, School of Public Health, University of Alabama at Birmingham, Birmingham, AL, USA.
Barbara BenoitMass General Brigham Research Information Science & Computing, Boston, MA, USA.
Chia-Yen ChenTranslational Biology, Biogen Inc., Cambridge, MA, USA.
Karmel W ChoiCenter for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA.
James J CiminoInformatics Institute, University of Alabama at Birmingham, Birmingham, AL, USA.
Brittney H DavisDepartment of Neurology, School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.
Ozan DikilitasDepartment of Cardiovascular Medicine, Mayo Clinic, Rochester, MN, USA.
Bethany EtheridgeDepartment of Neurology, School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.
Yen-Chen Anne FengCenter for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA.
Vivian GainerMass General Brigham Research Information Science & Computing, Boston, MA, USA.
Hailiang HuangBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Gail P JarvikDivision of Medical Genetics, Department of Medicine, University of Washington, Seattle, WA, USA.
Christopher KachulisBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Eimear E KennyInstitute for Genomic Health, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Atlas KhanDivision of Nephrology, Department of Medicine, Vagelos College of Physicians & Surgeons, Columbia University, New York, USA.
Krzysztof KirylukDivision of Nephrology, Department of Medicine, Vagelos College of Physicians & Surgeons, Columbia University, New York, USA.
Leah KottyanCenter for Autoimmune Genomics and Etiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Iftikhar J KulloDepartment of Cardiovascular Medicine, Mayo Clinic, Rochester, MN, USA.
Christoph LangeDepartment of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Niall LennonBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Aaron LeongBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Edyta MalolepszaBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Ayme D MilesInformatics Institute, University of Alabama at Birmingham, Birmingham, AL, USA.
Shawn MurphyDepartment of Neurology, Massachusetts General Hospital, Boston, MA, USA.
Bahram NamjouCenter for Autoimmune Genomics and Etiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Renuka NarayanDepartment of Neurology, School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.
Mark J O'ConnorUMass Memorial Health Care, Worcester, MA, USA.
Jennifer A PachecoCenter for Genetic Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
Emma PerezDepartment of Medicine, Brigham and Women's Hospital, Boston, MA, USA.
Laura J Rasmussen-TorvikDepartment of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
Elisabeth A RosenthalDivision of Medical Genetics, Department of Medicine, University of Washington, Seattle, WA, USA.
Daniel SchaidDepartment of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, USA.
Maria StamouDivision of Endocrinology, Massachusetts General Hospital, Boston, MA, USA.
Miriam S UdlerCenter for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA.
Wei-Qi WeiDepartment of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, TN, USA.
Scott T WeissChanning Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.
Maggie C Y NgVanderbilt Genetics Institute, Division of Genetic Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
Jordan W SmollerCenter for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA.
Matthew S LeboBroad Institute of MIT and Harvard, Cambridge, MA, USA.
James B MeigsBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Nita A LimdiDepartment of Neurology, School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.
Elizabeth W KarlsonDepartment of Medicine, Brigham and Women's Hospital, Boston, MA, USA.
University of Alabama at Birmingham · USBroad Institute · USBrigham and Women's Hospital · USMassachusetts General Hospital · USCincinnati Children's Hospital Medical Center · USColumbia University · USMass General Brigham · USNorthwestern University · USUniversity of Washington Medical Center · USVanderbilt University Medical Center · USBiogen (United States) · USGenomic Health (United States) · USHarvard University · USMayo Clinic · USMayo Clinic in Arizona · USMayo Clinic in Florida · USNational Taiwan University · TWNational Yang Ming Chiao Tung University · TWUMass Memorial Health Care · US

Funding

VCID and Stroke in a Bi-racial National CohortU01NS041588 · NINDS · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI CUSHMAN, MARY, HOWARD, GEORGE · 2002 to 2022
$96.0M
Genomic Basis of Susceptibility to COVID-19 Infection and its ComplicationsU01HG006379 · NHGRI · MAYO CLINIC ROCHESTER · PI Richard R. Sharp · 2011 to 2026
$16.5M
Finding Genomic Profiles of COVID-19 Phenotypes from the EHRU01HG008685 · NHGRI · BRIGHAM AND WOMEN'S HOSPITAL · PI ELIZABETH W KARLSON, Matthew S Lebo · 2015 to 2026
$13.6M
Integrating Genomic Risk Assessment for Disease Management in a Clinical PopulationU01HG011167 · NHGRI · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI JAMES J CIMINO, NITA A LIMDI · 2020 to 2026
$9.3M
Polygenic Risk Scores for Healthier African American FamiliesU01HG011172 · NHGRI · CINCINNATI CHILDRENS HOSP MED CTR · PI Leah Claire Kottyan, LISA J MARTIN · 2020 to 2026
$7.2M
Development of Polygenic Risk Scores for Diabetes and Complications across the Life-Span in Populations of Multiple AncestriesU01HG011723 · NHGRI · BROAD INSTITUTE, INC. · PI Alisa Knodle Manning, Josep Maria Mercader · 2021 to 2026
$5.7M
Cardiorenal Genomics for Risk Prediction in African Descent PopulationsR35HL155466 · NHLBI · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI Marguerite R Irvin · 2021 to 2026
$5.1M
A Personalized Genomic Medicine Pilot Program Using the NJgene eMERGE ExperienceU01HG006388 · NHGRI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI CHISHOLM, REX L, SMITH, MAUREEN E · 2011 to 2014
$4.1M
Genetic Discovery and Application in a Clinical Setting Continuing a PartnershipU01HG006375 · NHGRI · KAISER FOUNDATION HEALTH PLAN OF WASHINGTON · PI JARVIK, GAIL PAIRITZ, LARSON, ERIC B · 2011 to 2014
$4.1M
TOPMed Omics of Type 2 Diabetes and Quantitative TraitsUM1DK078616 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI MANNING, ALISA KNODLE · 2021 to 2025
$3.8M
Integrative Analysis of a GWAS Repository with EMRs from over 40,000 ChildrenU01HG006830 · NHGRI · CHILDREN'S HOSP OF PHILADELPHIA · PI HAKONARSON, HAKON · 2012 to 2014
$3.7M
Genomic Background of Blood Pressure Response to Thiazide Diuretic in African AmericansR01HL123782 · NHLBI · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI IRVIN, MARGUERITE R · 2016 to 2020
$3.7M
NHGRI NIH HHS U01 HG006375NHGRI NIH HHS U01 HG006379NHGRI NIH HHS U01 HG006388NHGRI NIH HHS U01 HG006830NHGRI NIH HHS U01 HG008685NHGRI NIH HHS U01HG008685NHGRI NIH HHS U01 HG011167NHGRI NIH HHS U01 HG011172NHGRI NIH HHS U01 HG011723NHLBI NIH HHS K24 HL133373NHLBI NIH HHS R01 HL123782NHLBI NIH HHS R01 HL136666NHLBI NIH HHS R35 HL155466NIA NIH HHS R00 AG054573NICHD NIH HHS F32 HD108873NIDDK NIH HHS K23 DK114551NIDDK NIH HHS K25 DK128563NIDDK NIH HHS R03 DK131249NIDDK NIH HHS U01 DK078616NIDDK NIH HHS UM1 DK078616NIGMS NIH HHS R35 GM140487NINDS NIH HHS U01 NS041588
6 · The paper itself

Abstract

backgroundType 2 diabetes (T2D) is a worldwide scourge caused by both genetic and environmental risk factors that disproportionately afflicts communities of color. Leveraging existing large-scale genome-wide association studies (GWAS), polygenic risk scores (PRS) have shown promise to complement established clinical risk factors and intervention paradigms, and improve early diagnosis and prevention of T2D. However, to date, T2D PRS have been most widely developed and validated in individuals of European descent. Comprehensive assessment of T2D PRS in non-European populations is critical for equitable deployment of PRS to clinical practice that benefits global populations.

methodsWe integrated T2D GWAS in European, African, and East Asian populations to construct a trans-ancestry T2D PRS using a newly developed Bayesian polygenic modeling method, and assessed the prediction accuracy of the PRS in the multi-ethnic Electronic Medical Records and Genomics (eMERGE) study (11,945 cases; 57,694 controls), four Black cohorts (5137 cases; 9657 controls), and the Taiwan Biobank (4570 cases; 84,996 controls). We additionally evaluated a post hoc ancestry adjustment method that can express the polygenic risk on the same scale across ancestrally diverse individuals and facilitate the clinical implementation of the PRS in prospective cohorts.

resultsThe trans-ancestry PRS was significantly associated with T2D status across the ancestral groups examined. The top 2% of the PRS distribution can identify individuals with an approximately 2.5-4.5-fold of increase in T2D risk, which corresponds to the increased risk of T2D for first-degree relatives. The post hoc ancestry adjustment method eliminated major distributional differences in the PRS across ancestries without compromising its predictive performance.

conclusionsBy integrating T2D GWAS from multiple populations, we developed and validated a trans-ancestry PRS, and demonstrated its potential as a meaningful index of risk among diverse patients in clinical settings. Our efforts represent the first step towards the implementation of the T2D PRS into routine healthcare.

Indexed as

Diabetes Mellitus, Type 2Genome-Wide Association StudyBayes TheoremGenetic Predisposition to DiseaseHumansProspective StudiesRisk FactorsClinical implementationDiverse populationsPolygenic risk scoreType 2 diabetes

Identifiers

PMID35765100
PMCPMC9241245
OpenAlexW4283712790

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.