| Title: | Mendelian randomization supports bidirectional causality between telomere length and clonal hematopoiesis of indeterminate potential |
| Journal: | Science Advances |
| Published: | 6 Apr 2022 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/35385311/ |
| DOI: | https://doi.org/10.1126/sciadv.abl6579 |
| URL: | https://www.science.org/doi/pdf/10.1126/sciadv.abl6579 |
| Citations: | 47 (29 in last 2 years) as of 8 Aug 2024 |
Publication 12431
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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.</p>
122 Authors
- Tetsushi Nakao
- Alexander G. Bick
- Margaret A. Taub
- Seyedeh M. Zekavat
- M. Uddin
- Abhishek Niroula
- Cara L. Carty
- John Lane
- Michael C. Honigberg
- Joshua S. Weinstock
- Akhil Pampana
- Christopher J. Gibson
- Gabriel K. Griffin
- Shoa L. Clarke
- Romit Bhattacharya
- Themistocles L. Assimes
- Leslie S. Emery
- Adrienne M. Stilp
- Quenna Wong
- Jai Broome
- Cecelia A. Laurie
- Alyna T. Khan
- Albert V. Smith
- Thomas W. Blackwell
- Veryan Codd
- Christopher P. Nelson
- Zachary T. Yoneda
- Juan M. Peralta
- Donald W. Bowden
- Marguerite R. Irvin
- Meher Boorgula
- Wei Zhao
- Lisa R. Yanek
- Kerri L. Wiggins
- James E. Hixson
- C. Charles Gu
- Gina M. Peloso
- Dan M. Roden
- Muagututi'a S. Reupena
- Chii-Min Hwu
- Dawn L. DeMeo
- Kari E. North
- Shannon Kelly
- Solomon K. Musani
- Joshua C. Bis
- Donald M. Lloyd-Jones
- Jill M. Johnsen
- Michael Preuss
- Russell P. Tracy
- Patricia A. Peyser
- Dandi Qiao
- Pinkal Desai
- Joanne E. Curran
- Barry I. Freedman
- Hemant K. Tiwari
- Sameer Chavan
- Jennifer A. Smith
- Nicholas L. Smith
- Tanika N. Kelly
- Bertha Hidalgo
- L. Adrienne Cupples
- Daniel E. Weeks
- Nicola L. Hawley
- Ryan L. Minster
- Lifestyle and Genetic Adaptations Study Group The Samoan Obesity
- Ranjan Deka
- Take T. Naseri
- Lisa de las Fuentes
- Laura M. Raffield
- Alanna C. Morrison
- Paul S. Vries
- Christie M. Ballantyne
- Eimear E. Kenny
- Stephen S. Rich
- Eric A. Whitsel
- Michael H. Cho
- M. Benjamin Shoemaker
- Betty S. Pace
- John Blangero
- Nicholette D. Palmer
- Braxton D. Mitchell
- Alan R. Shuldiner
- Kathleen C. Barnes
- Susan Redline
- Sharon L.R. Kardia
- Gonçalo R. Abecasis
- Lewis C. Becker
- Susan R. Heckbert
- Jiang He
- Wendy Post
- Donna K. Arnett
- Ramachandran S. Vasan
- Dawood Darbar
- Scott T. Weiss
- Stephen T. McGarvey
- Mariza de Andrade
- Yii-Der Ida Chen
- Robert C. Kaplan
- Deborah A. Meyers
- Brian S. Custer
- Adolfo Correa
- Bruce M. Psaty
- Myriam Fornage
- JoAnn E. Manson
- Eric Boerwinkle
- Barbara A. Konkle
- Ruth J.F. Loos
- Jerome I. Rotter
- Edwin K. Silverman
- Charles Kooperberg
- John Danesh
- Nilesh J. Samani
- Siddhartha Jaiswal
- Peter Libby
- Patrick T. Ellinor
- Nathan Pankratz
- Benjamin L. Ebert
- Alexander P. Reiner
- Rasika A. Mathias
- Ron Do
- NHLBI Trans-Omics for Precision Medicine Consortium
- 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