@article{653f77d3f3a640e7b3fcce591e243e97,
title = "Mendelian randomization supports bidirectional causality between telomere length and clonal hematopoiesis of indeterminate potential",
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.",
author = "{The Samoan Obesity, Lifestyle and Genetic Adaptations Study (OLaGA) Group} and {NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium} and Tetsushi Nakao and Bick, {Alexander G.} and Taub, {Margaret A.} and Zekavat, {Seyedeh M.} and Uddin, {Md M.} and Abhishek Niroula and Carty, {Cara L.} and John Lane and Honigberg, {Michael C.} and Weinstock, {Joshua S.} and Akhil Pampana and Gibson, {Christopher J.} and Griffin, {Gabriel K.} and Clarke, {Shoa L.} and Romit Bhattacharya and Assimes, {Themistocles L.} and Emery, {Leslie S.} and Stilp, {Adrienne M.} and Quenna Wong and Jai Broome and Laurie, {Cecelia A.} and Khan, {Alyna T.} and Smith, {Albert V.} and Blackwell, {Thomas W.} and Veryan Codd and Nelson, {Christopher P.} and Yoneda, {Zachary T.} and Peralta, {Juan M.} and Bowden, {Donald W.} and Irvin, {Marguerite R.} and Meher Boorgula and Wei Zhao and Yanek, {Lisa R.} and Wiggins, {Kerri L.} and Hixson, {James E.} and {Charles Gu}, C. and Peloso, {Gina M.} and Roden, {Dan M.} and Reupena, {Muagututi'a S.} and Hwu, {Chii Min} and DeMeo, {Dawn L.} and North, {Kari E.} and Shannon Kelly and Musani, {Solomon K.} and Bis, {Joshua C.} and Lloyd-Jones, {Donald M.} and Johnsen, {Jill M.} and Michael Preuss and Tracy, {Russell P.} and Peyser, {Patricia A.} and Dandi Qiao and Pinkal Desai and Curran, {Joanne E.} and Freedman, {Barry I.} and Tiwari, {Hemant K.} and Sameer Chavan and Smith, {Jennifer A.} and Smith, {Nicholas L.} and Kelly, {Tanika N.} and Bertha Hidalgo and {Adrienne Cupples}, L. and Weeks, {Daniel E.} and Hawley, {Nicola L.} and Minster, {Ryan L.} and Ranjan Deka and Naseri, {Take T.} and {de las Fuentes}, Lisa and Raffield, {Laura M.} and Morrison, {Alanna C.} and Vries, {Paul S.} and Ballantyne, {Christie M.} and Kenny, {Eimear E.} and Rich, {Stephen S.} and Whitsel, {Eric A.} and Cho, {Michael H.} and {Benjamin Shoemaker}, M. and Pace, {Betty S.} and John Blangero and Palmer, {Nicholette D.} and Mitchell, {Braxton D.} and Shuldiner, {Alan R.} and Barnes, {Kathleen C.} and Susan Redline and Kardia, {Sharon L.R.} and Abecasis, {Gon{\c c}alo R.} and Becker, {Lewis C.} and Heckbert, {Susan R.} and Jiang He and Wendy Post and Arnett, {Donna K.} and Vasan, {Ramachandran S.} and Dawood Darbar and Weiss, {Scott T.} and McGarvey, {Stephen T.} and {de Andrade}, Mariza and Chen, {Yii Der Ida} and Kaplan, {Robert C.} and Meyers, {Deborah A.} and Custer, {Brian S.} and Adolfo Correa and Psaty, {Bruce M.} and Myriam Fornage and Manson, {Jo Ann E.} and Eric Boerwinkle and Konkle, {Barbara A.} and Loos, {Ruth J.F.} and Rotter, {Jerome I.} and Silverman, {Edwin K.} and Charles Kooperberg and John Danesh and Samani, {Nilesh J.} and Siddhartha Jaiswal and Peter Libby and Ellinor, {Patrick T.} and Nathan Pankratz and Ebert, {Benjamin L.} and Reiner, {Alexander P.} and Mathias, {Rasika A.} and Ron Do and Pradeep Natarajan",
note = "Publisher Copyright: Copyright {\textcopyright} 2022 The Authors, some rights reserved;",
year = "2022",
month = apr,
doi = "10.1126/sciadv.abl6579",
language = "English",
volume = "8",
journal = "Science Advances",
issn = "2375-2548",
number = "14",
}