Mayo Clinic - AuthorCitation

Mendelian randomization supports bidirectional causality between telomere length and clonal hematopoiesis of indeterminate potential

Nakao, Tetsushi , Bick, Alexander G. , Taub, Margaret A. , Uddin, Md Mesbah , Niroula, Abhishek , Carty, Cara L. , Lane, John , Honigberg, Michael C. , Weinstock, Joshua S. , Pampana, Akhil , Griffin, Gabriel K. , Bhattacharya, Romit , Assimes, Themistocles L. , Emery, Leslie S. , Wong, Quenna , Broome, Jai , Laurie, Cecelia , Khan, Alyna , Smith, Albert V. , Blackwell, Thomas W. , Nelson, Christopher P. , Yoneda, Zachary T. , Peralta, Juan M. , Bowden, Donald W. , Irvin, Marguerite R. , Boorgula, Meher Preethi, Zhao, Wei , Yanek, Lisa R. , Roden, Dan M. , Reupena, Muagututi‘a Sefuiva , DeMeo, Dawn L. , Kelly, Shannon , Musani, Solomon K., Bis, Joshua C. , Lloyd‐Jones, Donald M. , Peyser, Patricia A. , Qiao, Dandi , Tiwari, Hemant K., Smith, Jennifer A. , Smith, Nicholas L. , Kelly, Tanika N. , Hidalgo, Bertha , Weeks, Daniel E. , Group, The Samoan Obesity, Lifestyle and Genetic Adaptations Study (OLaGA), Deka, Ranjan , Naseri, Take, Fuentes, Lisa de las , Raffield, Laura M. , Morrison, Alanna C. , Vries, Paul S. de , Shoemaker, M. Benjamin , Palmer, Nicholette D. , Barnes, Kathleen C. , Redline, Susan , Kardia, Sharon L.R., Becker, Lewis C. , Heckbert, Susan R. , He, Jiang , Post, Wendy S. , Arnett, Donna K. , McGarvey, Stephen T. , Chen, Yii‐Der Ida , Kaplan, Robert C. , Meyers, Deborah A. , Fornage, Myriam , Boerwinkle, Eric , Loos, Ruth J. F. , Silverman, Edwin K. , Danesh, John , Samani, Nilesh J. , Jaiswal, Siddhartha , Ebert, Benjamin L. , Reiner, Alex P. , Mathias, Rasika A. , Do, Ron , Natarajan, Pradeep , Zhao, Wei , Zekavat, Seyedeh M , Uddin, Md M , Niroula, Abhishek , Lane, John , Honigberg, Michael C , Weinstock, Joshua S , Pampana, Akhil , Griffin, Gabriel K , Clarke, Shoa L , Bhattacharya, Romit , Assimes, Themistocles L , Emery, Leslie S , Stilp, Adrienne M , Wong, Quenna , Broome, Jai , Khan, Alyna T , Smith, Albert V , Codd, Veryan , Nelson, Christopher P , Yoneda, Zachary T , Peralta, Juan M , Yanek, Lisa R , Wiggins, Kerri L , Gu, C Charles , Peloso, Gina M , Roden, Dan M. , Hwu, Chii-Min , North, Kari E. , Bis, Joshua C , Lloyd-Jones, Donald M , Johnsen, Jill M , Preuss, Michael , Tracy, Russell P , Peyser, Patricia A , Qiao, Dandi , Curran, Joanne E , Freedman, Barry I , Chavan, Sameer , Smith, Jennifer A , Kelly, Tanika N , Hidalgo, Bertha , Weeks, Daniel E , Hawley, Nicola L , Minster, Ryan L , de las Fuentes, Lisa , Raffield, Laura M , Ballantyne, Christie M , Kenny, Eimear E , Rich, Stephen S , Whitsel, Eric A , Cho, Michael H , Palmer, Nicholette D , Mitchell, Braxton D , Shuldiner, Alan R , Redline, Susan , Heckbert, Susan R , He, Jiang , Post, Wendy , Arnett, Donna K , Vasan, Ramachandran S , Weiss, Scott T , McGarvey, Stephen T , Custer, Brian S , Correa, Adolfo , Manson, JoAnn E , Konkle, Barbara A , Loos, Ruth J F , Rotter, Jerome I , Silverman, Edwin K , Kooperberg, Charles , Samani, Nilesh J , Jaiswal, Siddhartha , Libby, Peter , Ellinor, Patrick T , Pankratz, Nathan , Ebert, Benjamin L , Mathias, Rasika A , Do, Ron , Natarajan, Pradeep , Morrison, Alanna C , Bick, Alexander G , Gibson, Christopher James , Clarke, Shoa L. , Codd, Veryan , Wiggins, Kerri L. , Hixson, James E. , Peloso, Gina M. , Tracy, Russell P. , Desai, Pinkal , Curran, Joanne E. , Freedman, Barry I. , Cupples, L. Adrienne , Group, The Samoan Obesity, Lifestyle and Genetic Adaptations Study (OLaGA), Naseri, Take K. , Ballantyne, Christie M. , Rich, Stephen S. , Cho, Michael H. , Pace, Betty S. , Blangero, John , Mitchell, Braxton D. , Shuldiner, Alan R. , Abecasis, Gonçalo R. , Vasan, Ramachandran S. , Darbar, Dawood , Weiss, Scott T. , Andrade, Mariza de , Custer, Brian , Psaty, Bruce M. , Manson, JoAnn E. , Konkle, Barbara A. , Rotter, Jerome I. , Kooperberg, Charles , Libby, Peter , Ellinor, Patrick T. , Pankratz, Nathan

Science Advances | April 6, 2022 | Volume: 8 | Issue: 14 | Pages: No page available

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.

Codd, Veryan

Citations 2

Mendelian randomization supports bidirectional causality between telomere length and clonal hematopoiesis of indeterminate potential

Longer genotypically-estimated leukocyte telomere length is associated with increased adult glioma risk