Evidence map›Paper›PMID 37148359›Full record

SynthesisDiabetologia2023

The power of TOPMed imputation for the discovery of Latino-enriched rare variants associated with type 2 diabetes.

Alicia Huerta-Chagoya, Philip Schroeder, Ravi Mandla, Aaron J Deutsch, Wanying Zhu, Lauren Petty, Xiaoyan Yi, Joanne B Cole, Miriam S Udler, Peter Dornbos and 54 more

Open access · hybridAbstract readMeta-Analysis
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in Diabetologia, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed, 1 pooled it
5.3field-weighted citation impact, top 4% 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

12 citing papers in PubMed, 1 synthesis or guideline pooled it, 17 citations in OpenAlex.

  1. Pooled it
  2. The impact of low-frequency genetic variants on serum protein levels.bioRxiv : the preprint server for biology · 2026
    Article
  3. Review
  4. Review
  5. Article
  6. Review
  7. Large-scale admixture mapping in themedRxiv : the preprint server for health sciences · 2025
    Article
  8. Article
  9. 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

64 authors at 20 institutions in 6 countries.

Alicia Huerta-ChagoyaPrograms in Metabolism and Medical & Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA, USA. ahuerta@broadinstitute.org.
Philip SchroederPrograms in Metabolism and Medical & Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
Ravi MandlaPrograms in Metabolism and Medical & Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
Aaron J DeutschPrograms in Metabolism and Medical & Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
Wanying ZhuVanderbilt Genetics Institute, Vanderbilt University Medical Center, Nashville, TN, USA.
Lauren PettyVanderbilt Genetics Institute, Vanderbilt University Medical Center, Nashville, TN, USA.
Xiaoyan YiULB Center for Diabetes Research, Medical Faculty, Université Libre de Bruxelles, Brussels, Belgium.
Joanne B ColePrograms in Metabolism and Medical & Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
Miriam S UdlerCenter for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA.
Peter DornbosPrograms in Metabolism and Medical & Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
Bianca PornealaDivision of General Internal Medicine, Massachusetts General Hospital, Boston, MA, USA.
Daniel DiCorpoDepartment of Biostatistics, Boston University School of Public Health, Boston, MA, USA.
Ching-Ti LiuDepartment of Biostatistics, Boston University School of Public Health, Boston, MA, USA.
Josephine H LiPrograms in Metabolism and Medical & Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
Lukasz SzczerbińskiPrograms in Metabolism and Medical & Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
Varinderpal KaurDiabetes Unit, Massachusetts General Hospital, Boston, MA, USA.
Joohyun KimVanderbilt Genetics Institute, Division of Genetic Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
Yingchang LuVanderbilt Genetics Institute, Division of Genetic Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
Alicia MartinPrograms in Metabolism and Medical & Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
Decio L EizirikULB Center for Diabetes Research, Medical Faculty, Université Libre de Bruxelles, Brussels, Belgium.
Piero MarchettiDepartment of Clinical and Experimental Medicine, and AOUP Cisanello University Hospital, University of Pisa, Pisa, Italy.
Lorella MarselliDepartment of Clinical and Experimental Medicine, and AOUP Cisanello University Hospital, University of Pisa, Pisa, Italy.
Ling ChenCenter for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA.
Shylaja SrinivasanDepartment of Pediatrics, University of California San Francisco, San Francisco, CA, USA.
Jennifer ToddDepartment of Pediatrics, University of Vermont, Burlington, VT, USA.
Jason FlannickPrograms in Metabolism and Medical & Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
Rose Gubitosi-KlugPediatric Endocrinology, Diabetes, and Metabolism, Case Western Reserve University and Rainbow Babies and Children's Hospital, Cleveland, OH, USA.
Lynne LevitskyDepartment of Pediatrics, Division of Pediatric Endocrinology and Pediatric Diabetes Center, Massachusetts General Hospital, Boston, MA, USA.
Rachana ShahPediatric Endocrinology and Diabetes, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Megan KelseyPediatric Endocrinology, University of Colorado School of Medicine, Aurora, CO, USA.
Brian BurkeBiostatistics Center, The George Washington University, Rockville, MD, USA.
Dana M DabeleaDepartment of Epidemiology, University of Colorado School of Medicine, Aurora, CO, USA.
Jasmin DiversNYU Langone Health, New York, NY, USA.
Santica MarcovinaMedpace Reference Laboratories, Cincinnati, OH, USA.
Lauren StalbowThe Charles Bronfman Institute of Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Ruth J F LoosThe Charles Bronfman Institute of Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Burcu F DarstDivision of Public Health Science, Fred Hutchinson Cancer Center, Seattle, WA, USA.
Charles KooperbergDivision of Public Health Science, Fred Hutchinson Cancer Center, Seattle, WA, USA.
Laura M RaffieldDepartment of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Christopher HaimanDepartment of Population and Public Health Sciences, University of Southern California, Los Angeles, CA, USA.
Quan SunDepartment of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Joseph B McCormickSchool of Public Health, The University of Texas Health Science Center at Houston, Brownsville, TX, USA.
Susan P Fisher-HochSchool of Public Health, The University of Texas Health Science Center at Houston, Brownsville, TX, USA.
Maria L OrdoñezUnidad de Biología Molecular y Medicina Genómica, Instituto Nacional de Ciencias Médicas y Nutrición, Mexico City, Mexico.
James MeigsPrograms in Metabolism and Medical & Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
Leslie J BaierPhoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Phoenix, AZ, USA.
Clicerio González-VillalpandoCentro de Estudios en Diabetes, Unidad de Investigacion en Diabetes y Riesgo Cardiovascular, Centro de Investigacion en Salud Poblacional, Instituto Nacional de Salud Pública, Mexico City, Mexico.
Maria Elena González-VillalpandoCentro de Estudios en Diabetes, Unidad de Investigacion en Diabetes y Riesgo Cardiovascular, Centro de Investigacion en Salud Poblacional, Instituto Nacional de Salud Pública, Mexico City, Mexico.
Lorena OrozcoLaboratorio Inmunogénomica y Enfermedades Metabólicas, Instituto Nacional de Medicina Genómica, Mexico City, Mexico.
Lourdes García-GarcíaInstituto Nacional de Salud Pública, Cuernavaca, Mexico.
Andrés Moreno-EstradaLaboratorio Nacional de Genómica para la Biodiversidad (LANGEBIO), Unidad de Genómica Avanzada (UGA), CINVESTAV, Irapuato, Mexico.
Mexican Biobank
Carlos A Aguilar-SalinasUnidad de Investigación de Enfermedades Metabólicas y Dirección de Nutrición, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico.
Teresa TusiéDepartamento de Medicina Genómica y Toxicología Ambiental, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Mexico City, Mexico.
Josée DupuisDepartment of Biostatistics, Boston University School of Public Health, Boston, MA, USA.
Maggie C Y NgVanderbilt Genetics Institute, Division of Genetic Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
Alisa ManningClinical and Translational Epidemiology Unit, Massachusetts General Hospital, Boston, MA, USA.
Heather M HighlandDepartment of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Miriam CnopULB Center for Diabetes Research, Medical Faculty, Université Libre de Bruxelles, Brussels, Belgium.
Robert HansonDiabetes Epidemiology and Clinical Research Section, National Institute of Diabetes and Digestive and Kidney Diseases, Phoenix, AZ, USA.
Jennifer BelowVanderbilt Genetics Institute, Vanderbilt University Medical Center, Nashville, TN, USA.
Jose C FlorezPrograms in Metabolism and Medical & Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
Aaron LeongPrograms in Metabolism and Medical & Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
Josep M MercaderPrograms in Metabolism and Medical & Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA, USA. mercader@broadinstitute.org.ORCID http://orcid.org/0000-0001-8494-3660
Broad Institute · USMassachusetts General Hospital · USBoston University · USUniversity of North Carolina at Chapel Hill · USVanderbilt University Medical Center · USInstituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán · MXInstituto Nacional de Salud Pública · MXUniversité Libre de Bruxelles · BEFred Hutch Cancer Center · USThe University of Texas Health Science Center at Houston · USUniversity of Colorado Denver · USUniversity of Pisa · ITCentro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional · MXChildren's Hospital of Philadelphia · USGeorge Washington University · USIcahn School of Medicine at Mount Sinai · USMedpace (United States) · USNational Institute of Diabetes and Digestive and Kidney Diseases · USNational Institute of Genomic Medicine · MXNational Institutes of Health · US

Funding

Technology to Empower Changes in Health (TECH) Network Participant Technologies CenterU24OD023176 · OD · SCRIPPS RESEARCH INSTITUTE, THE · PI Eric Jeffrey Topol · 2021 to 2021
$52.3M
Precision Medicine Initiative Cohort Program BiobankU24OD023121 · OD · MAYO CLINIC ROCHESTER · PI Mine Cicek, Travis Henry · 2023 to 2023
$35.4M
Data and Research Support CenterU2COD023196 · OD · VANDERBILT UNIVERSITY MEDICAL CENTER · PI DAVID GLAZER, Paul A. Harris · 2022 to 2022
$16.0M
VALIDATION OF A DIET HISTORY METHOD FOR EPIDEMIOLOGIC STUDIES OF CANCERP01CA033619 · UNIVERSITY OF HAWAII AT MANOA · 1985 to 2004
$14.1M
The next iteration of the AMP-T2D Knowledge PortalUM1DK105554 · NIDDK · BROAD INSTITUTE, INC. · 2024 to 2025
$7.5M
Breast &Prostate Cancer &Hormone-related Gene VariantsU01CA098758 · UNIVERSITY OF SOUTHERN CALIFORNIA · 2003 to 2005
$6.5M
Multiethnic Cohort Study of Diet and CancerR37CA054281 · UNIVERSITY OF HAWAII AT MANOA · 2003 to 2005
$6.4M
Polygenic Risk Scores for Diverse Populations - Bridging Research and Clinical CareR01HL151152 · NHLBI · FRED HUTCHINSON CANCER CENTER · PI Christopher R Gignoux, Charles L Kooperberg · 2023 to 2023
$5.2M
Understanding Population Differences in Cancer: The MEC StudyU01CA164973 · UNIVERSITY OF HAWAII AT MANOA · 2025 to 2025
$4.9M
TRAINING PROGRAM IN ENDOCRINOLOGY AND DIABETEST32DK007028 · MASSACHUSETTS GENERAL HOSPITAL · 1986 to 2025
$4.2M
TOPMed Omics of Type 2 Diabetes and Quantitative TraitsUM1DK078616 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · 2022 to 2025
$3.1M
Healthy Americas: All of Us Research ProgramOT2OD025277 · NATIONAL ALLIANCE FOR HISPANIC HEALTH · 2025 to 2025
$3.0M
NCI NIH HHS P01 CA033619NCI NIH HHS R37 CA054281NCI NIH HHS U01 CA098758NCI NIH HHS U01 CA136792NCI NIH HHS U01 CA164973NHGRI NIH HHS R01 HG010297NHGRI NIH HHS U01 HG007376NHGRI NIH HHS U01 HG007397NHGRI NIH HHS U01 HG007416NHGRI NIH HHS U01 HG007417NHGRI NIH HHS U01 HG007419NHGRI NIH HHS U01 HG011723NHLBI NIH HHS K24 HL157960NHLBI NIH HHS N01HC65233NHLBI NIH HHS N01HC65234NHLBI NIH HHS N01HC65235NHLBI NIH HHS N01HC65236NHLBI NIH HHS N01HC65237NHLBI NIH HHS R01 HL142302NHLBI NIH HHS R01 HL142825NHLBI NIH HHS R01 HL151152NHLBI NIH HHS R01 HL151855NHLBI NIH HHS R01 HL158884NHLBI NIH HHS R56 HL150186NHLBI NIH HHS T32 HL129982NIA NIH HHS HHSN271201100004CNIDDK NIH HHS K99 DK127196NIDDK NIH HHS R01 DK125490NIDDK NIH HHS R01 DK127084NIDDK NIH HHS T32 DK007028NIDDK NIH HHS UM1 DK078616NIDDK NIH HHS UM1 DK105554NIDDK NIH HHS UM1 DK126185NIGMS NIH HHS R01 GM133169NIH HHS OT2 OD023205NIH HHS OT2 OD023206NIH 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 OD026553NIH HHS OT2 OD026554NIH HHS OT2 OD026555NIH HHS OT2 OD026556NIH HHS OT2 OD026557NIH HHS U24 OD023121NIH HHS U24 OD023163NIH HHS U24 OD023176NIH HHS U2C OD023196WHI NIH HHS HHSN268201100002CWHI NIH HHS HHSN268201100003CWHI NIH HHS HHSN268201100004C
6 · The paper itself

Abstract

aims/hypothesisThe Latino population has been systematically underrepresented in large-scale genetic analyses, and previous studies have relied on the imputation of ungenotyped variants based on the 1000 Genomes (1000G) imputation panel, which results in suboptimal capture of low-frequency or Latino-enriched variants. The National Heart, Lung, and Blood Institute (NHLBI) Trans-Omics for Precision Medicine (TOPMed) released the largest multi-ancestry genotype reference panel representing a unique opportunity to analyse rare genetic variations in the Latino population. We hypothesise that a more comprehensive analysis of low/rare variation using the TOPMed panel would improve our knowledge of the genetics of type 2 diabetes in the Latino population.

methodsWe evaluated the TOPMed imputation performance using genotyping array and whole-exome sequence data in six Latino cohorts. To evaluate the ability of TOPMed imputation to increase the number of identified loci, we performed a Latino type 2 diabetes genome-wide association study (GWAS) meta-analysis in 8150 individuals with type 2 diabetes and 10,735 control individuals and replicated the results in six additional cohorts including whole-genome sequence data from the All of Us cohort.

resultsCompared with imputation with 1000G, the TOPMed panel improved the identification of rare and low-frequency variants. We identified 26 genome-wide significant signals including a novel variant (minor allele frequency 1.7%; OR 1.37, p=3.4 × 10 CONCLUSIONS/

interpretationOur results demonstrate the utility of TOPMed imputation for identifying low-frequency variants in understudied populations, leading to the discovery of novel disease associations and the improvement of polygenic scores. DATA AVAILABILITY: Full summary statistics are available through the Common Metabolic Diseases Knowledge Portal ( https://t2d.hugeamp.org/downloads.html ) and through the GWAS catalog ( https://www.ebi.ac.uk/gwas/ , accession ID: GCST90255648). Polygenic score (PS) weights for each ancestry are available via the PGS catalog ( https://www.pgscatalog.org , publication ID: PGP000445, scores IDs: PGS003443, PGS003444 and PGS003445).

Indexed as

Diabetes Mellitus, Type 2Population HealthGenome-Wide Association StudyGenotypeHispanic or LatinoHumansPolymorphism, Single NucleotidePrecision MedicineGWAS meta-analysisLatino populationPolygenic scoreTOPMed imputationType 2 diabetes

Identifiers

PMID37148359
PMCPMC10244266
OpenAlexW4372354995

What Socratic holds

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Registered trials

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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 Socratic graph.