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Mendelian randomiza...
Mendelian randomization supports bidirectional causality between telomere length and clonal hematopoiesis of indeterminate potential
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- Nakao, T. (författare)
- Brigham and Women's Hospital / Harvard Medical School,Broad Institute,Massachusetts General Hospital,Dana-Farber Cancer Institute
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- Niroula, A. (författare)
- Lund University,Lunds universitet,Hematogenomics,Forskargrupper vid Lunds universitet,Lund University Research Groups,Broad Institute,Dana-Farber Cancer Institute
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- Do, Ron (författare)
- Icahn School of Medicine at Mount Sinai
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(creator_code:org_t)
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- American Association for the Advancement of Science (AAAS), 2022
- 2022
- Engelska.
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Ingår i: Science Advances. - : American Association for the Advancement of Science (AAAS). - 2375-2548. ; 8:14
- Relaterad länk:
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http://dx.doi.org/10... (free)
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- 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. Copyright © 2022 The Authors, some rights reserved;
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medical Genetics (hsv//eng)
Nyckelord
- Blood
- Chromosomes
- Computer aided design
- Random processes
- Causal relationships
- Coronary artery disease
- Genetic studies
- Haematopoiesis
- Hematopoietic cell
- Human genetics
- Leucocytes
- Mixed effects
- Randomisation
- Telomere length
- Diseases
Publikations- och innehållstyp
- art (ämneskategori)
- ref (ämneskategori)
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