| Title: | Human plasma proteomic profile of clonal hematopoiesis |
| Journal: | Nature Communications |
| Published: | 27 Nov 2025 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/41309676/ |
| DOI: | https://doi.org/10.1038/s41467-025-66755-z |
| URL: | https://www.nature.com/articles/s41467-025-66755-z_reference.pdf |
Publication 17288
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Abstract
Plasma proteomic profiles associated with subclinical somatic mutations in blood cells may offer insights into downstream clinical consequences. Here we explore these patterns in clonal hematopoiesis of indeterminate potential (CHIP), which is linked to several cancer and non-cancer outcomes, including coronary artery disease (CAD). Among 61,833 participants (3881 with CHIP) from TOPMed and UK Biobank (UKB) with blood-based DNA sequencing and proteomic measurements (1,148 proteins by SomaScan in TOPMed and 2917 proteins by Olink in UKB), we identify 32 and 345 proteins from TOPMed and UKB, respectively, associated with CHIP and most prevalent driver genes (DNMT3A, TET2, and ASXL1). These associations show substantial heterogeneity by driver genes, sex, and race, and were enriched for immune response and inflammation pathways. Mendelian randomization in humans, coupled with ELISA in hematopoietic Tet2-/- vs wild-type mice validation, disentangle causal proteomic perturbations from TET2 CHIP. Lastly, we identify plasma proteins shared between CHIP and CAD.</p>
52 Authors
- Zhi Yu
- Amélie Vromman
- Ngoc Quynh H. Nguyen
- Art Schuermans
- Linke Li
- Thiago Rentz
- Tetsushi Nakao
- Shamsudheen K. Vellarikkal
- Md Mesbah Uddin
- Abhishek Niroula
- Gabriel Griffin
- Michael C. Honigberg
- Amy E. Lin
- Christopher J. Gibson
- Daniel H. Katz
- Usman A. Tahir
- Shi Fang
- Jacqueline S. Dron
- Michael Pan
- Sara Haidermota
- Shriienidhie Ganesh
- Tajmara Antoine
- Joshua Weinstock
- Thomas R. Austin
- Ramachandran S. Vasan
- Gina M. Peloso
- Whitney Hornsby
- Peter Ganz
- JoAnn E. Manson
- Bernhard Haring
- Charles Kooperberg
- Alexander P. Reiner
- Joshua C. Bis
- Bruce M. Psaty
- Yuan-I Min
- Adolfo Correa
- Leslie A. Lange
- Wendy S. Post
- Jerome I. Rotter
- Stephen S. Rich
- James G. Wilson
- Benjamin L. Ebert
- Bing Yu
- Christie M. Ballantyne
- Josef Coresh
- Vijay G. Sankaran
- Alexander G. Bick
- Siddhartha Jaiswal
- Robert E. Gerszten
- Peter Libby
- Rajat M. Gupta
- Pradeep Natarajan
1 Application
| Application ID | Title |
|---|---|
| 7089 | Exome Sequencing of All Premature Coronary Artery Disease Participants in UK Biobank |
Enabling scientific discoveries that improve human health