Evidence map›Paper›PMID 36652671›Full record

ArticleBlood2023

A practical approach to curate clonal hematopoiesis of indeterminate potential in human genetic data sets.

Caitlyn Vlasschaert, Taralynn Mack, J Brett Heimlich, Abhishek Niroula, Md Mesbah Uddin, Joshua Weinstock, Brian Sharber, Alexander J Silver, Yaomin Xu, Michael Savona and 7 more

Open access · bronzeAbstract read
In one paragraph

Article in Blood, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 160 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
160citing papers in PubMed, 1 pooled it
38.1field-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

160 citing papers in PubMed, 1 synthesis or guideline pooled it, 131 citations in OpenAlex.

  1. Pooled it
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  7. Practical integration of ctDNA-defined minimal residual disease in gastrointestinal cancers: testing windows and evidence-aligned management frameworks.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026
    Review
  8. Article
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  11. medRxiv : the preprint server for health sciences · 2026
    Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Risk factors of clonal hematopoiesis of indeterminate potential.Clinical medicine (London, England) · 2026
    Article
  17. Article
  18. Review
  19. Article
  20. Article

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

17 authors at 8 institutions in 3 countries.

Caitlyn VlasschaertDepartment of Medicine, Queen's University, Kingston, ON, Canada.
Taralynn MackDivision of Genetic Medicine, Vanderbilt University Medical Center, Nashville, TN.ORCID 0000-0003-1043-2950
J Brett HeimlichDivision of Cardiology, Vanderbilt University Medical Center, Nashville, TN.ORCID 0000-0003-2812-5326
Abhishek NiroulaBroad Institute of MIT and Harvard, Cambridge, MA.
Md Mesbah UddinBroad Institute of MIT and Harvard, Cambridge, MA.ORCID 0000-0003-1846-0411
Joshua WeinstockCenter for Statistical Genetics, Department of Biostatistics - University of Michigan School of Public Health, Ann Arbor, MI.ORCID 0000-0001-7013-1899
Brian SharberDivision of Genetic Medicine, Vanderbilt University Medical Center, Nashville, TN.
Alexander J SilverProgram in Cancer Biology, Vanderbilt University School of Medicine, Nashville, TN.ORCID 0000-0001-8255-3140
Yaomin XuDepartment of Biomedical Informatics, Vanderbilt University School of Medicine, Nashville, TN.ORCID 0000-0002-3752-4006
Michael SavonaProgram in Cancer Biology, Vanderbilt University School of Medicine, Nashville, TN.
Christopher GibsonDepartment of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA.
Matthew B LanktreeDivision of Nephrology, St. Joseph's Healthcare Hamilton, Hamilton, ON, Canada.ORCID 0000-0002-5750-6286
Michael J RauhDepartment of Pathology and Molecular Medicine, Queen's University, Kingston, ON, Canada.ORCID 0000-0002-8346-5537
Benjamin L EbertBroad Institute of MIT and Harvard, Cambridge, MA.ORCID 0000-0003-0197-5451
Pradeep NatarajanBroad Institute of MIT and Harvard, Cambridge, MA.ORCID 0000-0001-8402-7435
Siddhartha JaiswalDepartment of Pathology, Stanford University, Palo Alto, CA.ORCID 0000-0002-9597-0477
Alexander G BickDivision of Genetic Medicine, Vanderbilt University Medical Center, Nashville, TN.
Broad Institute · USVanderbilt University · USVanderbilt University Medical Center · USQueen's University · CAHarvard University · USImpact · CAPalo Alto University · USUniversity of Michigan · US

Funding

Tumor Immunology and Microenvironment Research ProgramP30CA068485 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI MATTHEW J TYSKA · 1995 to 2026
$172.8M
Clonal hematopoiesis in humans: determinants of development and progressionR01HL148050 · NHLBI · BAYLOR COLLEGE OF MEDICINE · PI BALLANTYNE, CHRISTIE MITCHELL, NATARAJAN, PRADEEP · 2019 to 2022
$5.9M
The role of clonal hematopoiesis in the development and therapy of myeloid malignanciesR35CA253125 · NCI · DANA-FARBER CANCER INST · PI EBERT, BENJAMIN LEVINE · 2020 to 2024
$4.9M
Development of a Phenotype-based Predictive Analytic for Acute Myeloid LeukemiaR01CA262287 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI Tomer M Mark, Michael R Savona · 2021 to 2026
$3.2M
Clonal hematopoiesis in human aging and diseaseDP2HL157540 · NHLBI · STANFORD UNIVERSITY · PI JAISWAL, SIDDHARTHA · 2020 to 2020
$2.4M
Targeting Clonal Hematopoiesis of Indeterminate Potential Using Human GeneticsDP5OD029586 · OD · VANDERBILT UNIVERSITY MEDICAL CENTER · PI BICK, ALEXANDER · 2020 to 2024
$2.3M
EARLY DETECTION OF CLONAL HEMATOPOIESIS AND LEUKEMIA ASSOCIATED MUTATIONS IN WTC EXPOSED FIREFIGHTERS AFTER THE 9/11 ATTACKSU01OH012271 · OH · ALBERT EINSTEIN COLLEGE OF MEDICINE · PI PREZANT, DAVID J, SAVONA, MICHAEL R · 2021 to 2023
$1.5M
Harnessing EHR-linked Genomics Data to Study Clonal Hematopoiesis and its Evolution to Inflammatory PhenotypesF30DK127699 · NIDDK · VANDERBILT UNIVERSITY · PI SILVER, ALEXANDER JAMES · 2020 to 2023
$166k
Medical Research Council MC_PC_17228Medical Research Council MC_QA137853NCI NIH HHS P30 CA068485NCI NIH HHS R01 CA262287NCI NIH HHS R35 CA253125NHLBI NIH HHS DP2 HL157540NHLBI NIH HHS R01 HL148050NIDDK NIH HHS F30 DK127699NIH HHS DP5 OD029586NIOSH CDC HHS U01 OH012271
6 · The paper itself

Abstract

Clonal hematopoiesis of indeterminate potential (CHIP) is a common form of age-related somatic mosaicism that is associated with significant morbidity and mortality. CHIP mutations can be identified in peripheral blood samples that are sequenced using approaches that cover the whole genome, the whole exome, or targeted genetic regions; however, differentiating true CHIP mutations from sequencing artifacts and germ line variants is a considerable bioinformatic challenge. We present a stepwise method that combines filtering based on sequencing metrics, variant annotation, and population-based associations to increase the accuracy of CHIP calls. We apply this approach to ascertain CHIP in ∼550 000 individuals in the UK Biobank complete whole exome cohort and the All of Us Research Program initial whole genome release cohort. CHIP ascertainment on this scale unmasks recurrent artifactual variants and highlights the importance of specialized filtering approaches for several genes, including TET2 and ASXL1. We show how small changes in filtering parameters can considerably increase CHIP misclassification and reduce the effect size of epidemiological associations. Our high-fidelity call set refines previous population-based associations of CHIP with incident outcomes. For example, the annualized incidence of myeloid malignancy in individuals with small CHIP clones is 0.03% per year, which increases to 0.5% per year among individuals with very large CHIP clones. We also find a significantly lower prevalence of CHIP in individuals of self-reported Latino or Hispanic ethnicity in All of Us, highlighting the importance of including diverse populations. The standardization of CHIP calling will increase the fidelity of CHIP epidemiological work and is required for clinical CHIP diagnostic assays.

Indexed as

Clonal HematopoiesisPopulation HealthHematopoiesisHuman GeneticsHumansMutation

Identifiers

PMID36652671
PMCPMC10273159
OpenAlexW4317356542

What OpenQuestion holds

Textmetadata
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.