School of Medicine Publications and Presentations
Document Type
Article
Publication Date
4-6-2022
Abstract
Human genetic studies support an inverse causal relationship between leukocyte telomere length (LTL) and coronary artery disease (CAD), but directionally mixed effects for LTL and diverse malignancies. Clonal hematopoiesis of indeterminate potential (CHIP), characterized by expansion of hematopoietic cells bearing leukemogenic mutations, predisposes both hematologic malignancy and CAD. TERT (which encodes telomerase reverse transcriptase) is the most significantly associated germline locus for CHIP in genome-wide association studies. Here, we investigated the relationship between CHIP, LTL, and CAD in the Trans-Omics for Precision Medicine (TOPMed) program (n = 63,302) and UK Biobank (n = 47,080). Bidirectional Mendelian randomization studies were consistent with longer genetically imputed LTL increasing propensity to develop CHIP, but CHIP then, in turn, hastens to shorten measured LTL (mLTL). We also demonstrated evidence of modest mediation between CHIP and CAD by mLTL. Our data promote an understanding of potential causal relationships across CHIP and LTL toward prevention of CAD.
Recommended Citation
Nakao, T., Bick, A. G., Taub, M. A., Zekavat, S. M., Uddin, M. M., Niroula, A., Carty, C. L., Lane, J., Honigberg, M. C., Weinstock, J. S., Pampana, A., Gibson, C. J., Griffin, G. K., Clarke, S. L., Bhattacharya, R., Assimes, T. L., Emery, L. S., Stilp, A. M., Wong, Q., Broome, J., … Natarajan, P. (2022). Mendelian randomization supports bidirectional causality between telomere length and clonal hematopoiesis of indeterminate potential. Science advances, 8(14), eabl6579. https://doi.org/10.1126/sciadv.abl6579
Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License
Publication Title
Human Genetics
DOI
10.1126/sciadv.abl6579
Academic Level
faculty
Mentor/PI Department
Office of Human Genetics
Comments
© 2022 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC)