{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T22:47:01Z","timestamp":1790203621970,"version":"4.1.0"},"reference-count":58,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"14","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2022,4,8]]},"abstract":"<jats:p>\n                    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.\n                    <jats:italic>TERT<\/jats:italic>\n                    (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                    <jats:italic>n<\/jats:italic>\n                    = 63,302) and UK Biobank (\n                    <jats:italic>n<\/jats:italic>\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.\n                  <\/jats:p>","DOI":"10.1126\/sciadv.abl6579","type":"journal-article","created":{"date-parts":[[2022,4,6]],"date-time":"2022-04-06T13:52:26Z","timestamp":1649253146000},"source":"Crossref","is-referenced-by-count":82,"title":["Mendelian randomization supports bidirectional causality between telomere length and clonal hematopoiesis of indeterminate potential"],"prefix":"10.1126","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9979-2682","authenticated-orcid":true,"given":"Tetsushi","family":"Nakao","sequence":"first","affiliation":[{"name":"Broad Institute of MIT and Harvard, Cambridge, MA, USA."},{"name":"Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA, USA."},{"name":"Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA."},{"name":"Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women\u2019s Hospital, Boston, MA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5824-9595","authenticated-orcid":true,"given":"Alexander G.","family":"Bick","sequence":"additional","affiliation":[{"name":"Broad Institute of MIT and Harvard, Cambridge, MA, USA."},{"name":"Division of Genetic Medicine, Department of Medicine, Vanderbilt University, Nashville, TN, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret A.","family":"Taub","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4026-8944","authenticated-orcid":true,"given":"Seyedeh M.","family":"Zekavat","sequence":"additional","affiliation":[{"name":"Yale University School of Medicine, New Haven, CT, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1846-0411","authenticated-orcid":true,"given":"Md M.","family":"Uddin","sequence":"additional","affiliation":[{"name":"Broad Institute of MIT and Harvard, Cambridge, MA, USA."},{"name":"Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5904-0635","authenticated-orcid":true,"given":"Abhishek","family":"Niroula","sequence":"additional","affiliation":[{"name":"Broad Institute of MIT and Harvard, Cambridge, MA, USA."},{"name":"Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA."},{"name":"Department of Laboratory Medicine, Lund University, Lund, Sweden."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6378-8195","authenticated-orcid":true,"given":"Cara L.","family":"Carty","sequence":"additional","affiliation":[{"name":"Initiative for Research and Education to Advance Community Health, Washington State University, Seattle, WA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3582-5825","authenticated-orcid":true,"given":"John","family":"Lane","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology, University of Minnesota Medical School, Minneapolis, MN, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8630-5021","authenticated-orcid":true,"given":"Michael C.","family":"Honigberg","sequence":"additional","affiliation":[{"name":"Broad Institute of MIT and Harvard, Cambridge, MA, USA."},{"name":"Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA, USA."},{"name":"Department of Medicine, Harvard Medical School, Boston, MA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7013-1899","authenticated-orcid":true,"given":"Joshua S.","family":"Weinstock","sequence":"additional","affiliation":[{"name":"Center for Statistical Genetics, Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, MI, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4167-0540","authenticated-orcid":true,"given":"Akhil","family":"Pampana","sequence":"additional","affiliation":[{"name":"Broad Institute of MIT and Harvard, Cambridge, MA, USA."},{"name":"Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher J.","family":"Gibson","sequence":"additional","affiliation":[{"name":"Department of Medicine, Harvard Medical School, Boston, MA, 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