Standard
Mendelian randomization supports bidirectional causality between telomere length and clonal hematopoiesis of indeterminate potential. / Nakao, Tetsushi; Bick, Alexander G.; Taub, Margaret A.; Zekavat, Seyedeh M.; Uddin, Md M.; Niroula, Abhishek; Carty, Cara L.; Lane, John; Honigberg, Michael C.; Weinstock, Joshua S.; Pampana, Akhil; Gibson, Christopher J.; Griffin, Gabriel K.; Clarke, Shoa L.; Bhattacharya, Romit; Assimes, Themistocles L.; Emery, Leslie S.; Stilp, Adrienne M.; Wong, Quenna; Broome, Jai; Laurie, Cecelia A.; Khan, Alyna T.; Smith, Albert V.; Blackwell, Thomas W.; Codd, Veryan; Nelson, Christopher P.; Yoneda, Zachary T.; Peralta, Juan M.; Bowden, Donald W.; Irvin, Marguerite R.; Boorgula, Meher; Zhao, Wei; Yanek, Lisa R.; Wiggins, Kerri L.; Hixson, James E.; Charles Gu, C.; Peloso, Gina M.; Roden, Dan M.; Reupena, Muagututi'a S.; Hwu, Chii Min; DeMeo, Dawn L.; North, Kari E.; Kelly, Shannon; Musani, Solomon K.; Bis, Joshua C.; Lloyd-Jones, Donald M.; Johnsen, Jill M.; Preuss, Michael; Tracy, Russell P.; Loos, Ruth J.F.; The Samoan Obesity, Lifestyle and Genetic Adaptations Study (OLaGA) Group; NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium.
In:
Science Advances, Vol. 8, No. 14, eabl6579, 2022.
Research output: Contribution to journal › Journal article › Research › peer-review
Harvard
Nakao, T, Bick, AG, Taub, MA, Zekavat, SM, Uddin, MM, Niroula, A, Carty, CL, Lane, J, Honigberg, MC, Weinstock, JS, Pampana, A, Gibson, CJ, Griffin, GK, Clarke, SL, Bhattacharya, R, Assimes, TL, Emery, LS, Stilp, AM, Wong, Q, Broome, J, Laurie, CA, Khan, AT, Smith, AV, Blackwell, TW, Codd, V, Nelson, CP, Yoneda, ZT, Peralta, JM, Bowden, DW, Irvin, MR, Boorgula, M, Zhao, W, Yanek, LR, Wiggins, KL, Hixson, JE, Charles Gu, C, Peloso, GM, Roden, DM, Reupena, MS, Hwu, CM, DeMeo, DL, North, KE, Kelly, S, Musani, SK, Bis, JC, Lloyd-Jones, DM, Johnsen, JM, Preuss, M, Tracy, RP
, Loos, RJF, The Samoan Obesity, Lifestyle and Genetic Adaptations Study (OLaGA) Group & NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium 2022, '
Mendelian randomization supports bidirectional causality between telomere length and clonal hematopoiesis of indeterminate potential',
Science Advances, vol. 8, no. 14, eabl6579.
https://doi.org/10.1126/sciadv.abl6579APA
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., ... NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium (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.abl6579Vancouver
Nakao T, Bick AG, Taub MA, Zekavat SM, Uddin MM, Niroula A et al.
Mendelian randomization supports bidirectional causality between telomere length and clonal hematopoiesis of indeterminate potential.
Science Advances. 2022;8(14). eabl6579.
https://doi.org/10.1126/sciadv.abl6579Author
Nakao, Tetsushi ; Bick, Alexander G. ; Taub, Margaret A. ; Zekavat, Seyedeh M. ; Uddin, Md M. ; Niroula, Abhishek ; Carty, Cara L. ; Lane, John ; Honigberg, Michael C. ; Weinstock, Joshua S. ; Pampana, Akhil ; Gibson, Christopher J. ; Griffin, Gabriel K. ; Clarke, Shoa L. ; Bhattacharya, Romit ; Assimes, Themistocles L. ; Emery, Leslie S. ; Stilp, Adrienne M. ; Wong, Quenna ; Broome, Jai ; Laurie, Cecelia A. ; Khan, Alyna T. ; Smith, Albert V. ; Blackwell, Thomas W. ; Codd, Veryan ; Nelson, Christopher P. ; Yoneda, Zachary T. ; Peralta, Juan M. ; Bowden, Donald W. ; Irvin, Marguerite R. ; Boorgula, Meher ; Zhao, Wei ; Yanek, Lisa R. ; Wiggins, Kerri L. ; Hixson, James E. ; Charles Gu, C. ; Peloso, Gina M. ; Roden, Dan M. ; Reupena, Muagututi'a S. ; Hwu, Chii Min ; DeMeo, Dawn L. ; North, Kari E. ; Kelly, Shannon ; Musani, Solomon K. ; Bis, Joshua C. ; Lloyd-Jones, Donald M. ; Johnsen, Jill M. ; Preuss, Michael ; Tracy, Russell P. ; Loos, Ruth J.F. ; The Samoan Obesity, Lifestyle and Genetic Adaptations Study (OLaGA) Group ; NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium. / Mendelian randomization supports bidirectional causality between telomere length and clonal hematopoiesis of indeterminate potential. In: Science Advances. 2022 ; Vol. 8, No. 14.
Bibtex
@article{08604409fcdf46418cf724fe6eb806d8,
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 = "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 Loos, {Ruth J.F.} and {The Samoan Obesity, Lifestyle and Genetic Adaptations Study (OLaGA) Group} and {NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium}",
note = "Publisher Copyright: Copyright {\textcopyright} 2022 The Authors, some rights reserved;",
year = "2022",
doi = "10.1126/sciadv.abl6579",
language = "English",
volume = "8",
journal = "Science advances",
issn = "2375-2548",
publisher = "American Association for the Advancement of Science",
number = "14",
}
RIS
TY - JOUR
T1 - Mendelian randomization supports bidirectional causality between telomere length and clonal hematopoiesis of indeterminate potential
AU - Nakao, Tetsushi
AU - Bick, Alexander G.
AU - Taub, Margaret A.
AU - Zekavat, Seyedeh M.
AU - Uddin, Md M.
AU - Niroula, Abhishek
AU - Carty, Cara L.
AU - Lane, John
AU - Honigberg, Michael C.
AU - Weinstock, Joshua S.
AU - Pampana, Akhil
AU - Gibson, Christopher J.
AU - Griffin, Gabriel K.
AU - Clarke, Shoa L.
AU - Bhattacharya, Romit
AU - Assimes, Themistocles L.
AU - Emery, Leslie S.
AU - Stilp, Adrienne M.
AU - Wong, Quenna
AU - Broome, Jai
AU - Laurie, Cecelia A.
AU - Khan, Alyna T.
AU - Smith, Albert V.
AU - Blackwell, Thomas W.
AU - Codd, Veryan
AU - Nelson, Christopher P.
AU - Yoneda, Zachary T.
AU - Peralta, Juan M.
AU - Bowden, Donald W.
AU - Irvin, Marguerite R.
AU - Boorgula, Meher
AU - Zhao, Wei
AU - Yanek, Lisa R.
AU - Wiggins, Kerri L.
AU - Hixson, James E.
AU - Charles Gu, C.
AU - Peloso, Gina M.
AU - Roden, Dan M.
AU - Reupena, Muagututi'a S.
AU - Hwu, Chii Min
AU - DeMeo, Dawn L.
AU - North, Kari E.
AU - Kelly, Shannon
AU - Musani, Solomon K.
AU - Bis, Joshua C.
AU - Lloyd-Jones, Donald M.
AU - Johnsen, Jill M.
AU - Preuss, Michael
AU - Tracy, Russell P.
AU - Loos, Ruth J.F.
AU - The Samoan Obesity, Lifestyle and Genetic Adaptations Study (OLaGA) Group
AU - NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium
N1 - Publisher Copyright:
Copyright © 2022 The Authors, some rights reserved;
PY - 2022
Y1 - 2022
N2 - 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.
AB - 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.
U2 - 10.1126/sciadv.abl6579
DO - 10.1126/sciadv.abl6579
M3 - Journal article
C2 - 35385311
AN - SCOPUS:85127658648
VL - 8
JO - Science advances
JF - Science advances
SN - 2375-2548
IS - 14
M1 - eabl6579
ER -
