{"entity": "researcher", "timestamp": "2026-10-10T11:18:43.103Z", "family": "Nakao", "given": "Tetsushi", "initials": "T", "orcid": "0000-0001-9979-2682", "affiliations": ["Broad Institute of MIT and Harvard, Cambridge, MA, USA.", "Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA, USA.", "Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.", "Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA."], "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/researcher/7e818cd4544c41c2a7fa91dbce13429e.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/researcher/7e818cd4544c41c2a7fa91dbce13429e"}}, "publications": [{"entity": "publication", "iuid": "bf6df9e11dba43d98d3f283fdc3302a4", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/bf6df9e11dba43d98d3f283fdc3302a4.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/bf6df9e11dba43d98d3f283fdc3302a4"}}, "title": "Clonal Hematopoiesis and Major Adverse Cardiac Events in People With HIV: Insights From the REPRIEVE Trial.", "authors": [{"family": "Xue", "given": "Liying", "initials": "L"}, {"family": "Bhattacharya", "given": "Romit", "initials": "R", "orcid": "0000-0002-0782-4753", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/adea681afe7c431c91b30900a92baf8f.json"}}, {"family": "Uddin", "given": "Md Mesbah", "initials": "MM", "orcid": "0000-0003-1846-0411", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/42f1ac7010c34ba997a3fd9e56c6a56a.json"}}, {"family": "Nakao", "given": "Tetsushi", "initials": "T", "orcid": "0000-0001-9979-2682", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/7e818cd4544c41c2a7fa91dbce13429e.json"}}, {"family": "Zou", "given": "Roger", "initials": "R", "orcid": "0000-0003-1338-6398", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/9c4cddede9054c1585a557247cd2c32d.json"}}, {"family": "Patel", "given": "Aniruddh", "initials": "A", "orcid": "0000-0001-7871-9638", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/b7bf68d8799f4946814bc4e6ea80ef2f.json"}}, {"family": "Haidermota", "given": "Sara", "initials": "S", "orcid": "0000-0002-8588-3388", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/78ed21c17b99495790f19b85531c29b3.json"}}, {"family": "Niroula", "given": "Abhishek", "initials": "A", "orcid": "0000-0002-5904-0635", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/05df7afc7a494ba5af8a378e5ffa53f0.json"}}, {"family": "Viscosi", "given": "Victoria", "initials": "V"}, {"family": "Postupaka", "given": "Darina", "initials": "D", "orcid": "0000-0003-4893-6265", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/d77a6443167d49de834411434e1d0b5f.json"}}, {"family": "Bhatnagar", "given": "Aarushi", "initials": "A", "orcid": "0009-0004-4699-6779", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/ca127e06c66d48e9bd4be7cb2b2238a4.json"}}, {"family": "Finneran", "given": "Phoebe", "initials": "P", "orcid": "0000-0001-8201-733X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/113e6ea36d2d4a9d8a7f90377acc31f6.json"}}, {"family": "Bernardo", "given": "Rachel", "initials": "R", "orcid": "0000-0001-7139-6899", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/c5a8588e727e4bfb80b622375ccd5d89.json"}}, {"family": "Diggs", "given": "Marissa R", "initials": "MR"}, {"family": "Fitch", "given": "Kathleen V", "initials": "KV", "orcid": "0000-0002-0541-3707", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/9925de23fac74c2bb76faaa538e9b6f8.json"}}, {"family": "Chu", "given": "Sarah M", "initials": "SM"}, {"family": "McCallum", "given": "Sara", "initials": "S", "orcid": "0000-0002-0289-1295", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/ee2cc7b68408411e9c7278416a08006e.json"}}, {"family": "Currier", "given": "Judith S", "initials": "JS", "orcid": "0000-0003-4279-4737", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/332c1eb440224e5d828ad3e378e10947.json"}}, {"family": "Fichtenbaum", "given": "Carl J", "initials": "CJ", "orcid": "0000-0002-6778-7253", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/8f33fe77cc70491aa7971e8a159bd879.json"}}, {"family": "Malvestutto", "given": "Carlos D", "initials": "CD", "orcid": "0000-0003-3156-2965", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/579e40a069684a539bd8a9aaeeb9f88b.json"}}, {"family": "Aberg", "given": "Judith A", "initials": "JA", "orcid": "0000-0001-8162-0284", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/e3306ed88f5d4fedaecd6e6b130ff242.json"}}, {"family": "Bloomfield", "given": "Gerald S", "initials": "GS", "orcid": "0000-0002-7176-1611", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/1d2f1345c72d441e98c065dcb4621102.json"}}, {"family": "Ribaudo", "given": "Heather J", "initials": "HJ", "orcid": "0000-0002-0394-3990", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/b304b28a37ac46a695a17dc359f09485.json"}}, {"family": "Zanni", "given": "Markella V", "initials": "MV", "orcid": "0000-0002-4711-3956", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/a2c49e94d43e4d9da2d85873013b6e71.json"}}, {"family": "Libby", "given": "Peter", "initials": "P", "orcid": "0000-0002-1502-502X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/39fb20acff0442bd92fc7931d3ee6cf9.json"}}, {"family": "Hornsby", "given": "Whitney", "initials": "W", "orcid": "0000-0002-0672-0338", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/a8ab7aefec20431caf36c130be364ec4.json"}}, {"family": "Lu", "given": "Michael T", "initials": "MT", "orcid": "0000-0003-4696-9610", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/1b4c2374e856464ab3a2c7bbf6cd0723.json"}}, {"family": "Douglas", "given": "Pamela S", "initials": "PS", "orcid": "0000-0001-9876-4049", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/48b7c5b425e542c78387242bdd4b2b53.json"}}, {"family": "Grinspoon", "given": "Steven K", "initials": "SK"}, {"family": "Natarajan", "given": "Pradeep", "initials": "P", "orcid": "0000-0001-8402-7435", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/fe8bd48c61c047cd8e61c35d9e9ac650.json"}}], "type": "journal article", "published": "2026-01-00", "journal": {"title": "Arterioscler. Thromb. Vasc. Biol.", "issn": "1524-4636", "volume": "46", "issue": "1", "pages": "168-177", "issn-l": "1079-5642"}, "abstract": "People with HIV (PWH) experience higher cardiovascular disease event rates not fully explained by traditional risk factors. Clonal hematopoiesis of indeterminate potential (CHIP), an emerging risk factor for cardiovascular disease in the general population, has been reported to be more prevalent in PWH.\n\nUsing high-coverage targeted CHIP sequencing in the REPRIEVE (Randomized Trial to Prevent Vascular Events in HIV) cardiovascular disease prevention trial, we investigated whether CHIP increases the risk of major adverse cardiovascular events (MACE) among PWH, as well as whether HIV-associated factors were associated with greater CHIP prevalence among PWH. We analyzed whole-exome and targeted sequencing from 4490 PWH without known cardiovascular disease; 1653 (36.8%) were female, and 2039 (45.4%) were Black. MACE was defined by including cardiovascular death, myocardial infarction, hospitalization for unstable angina, stroke, transient ischemic attack, peripheral artery disease, revascularization, or death from an undetermined cause.\n\nA total of 837 (18.6%) had CHIP driver mutations, with 385 (8.6%) at variant allele fraction \u22652% and 61 (1.4%) at variant allele fraction \u226510%. Although overall CHIP was not associated with MACE, the presence of large CHIP (variant allele fraction \u226510%) was associated with increased odds for the first occurrence of myocardial infarction or cardiac catheterization, or revascularization, despite low overall event rates. Adjustments for pitavastatin treatment did not attenuate this association. Furthermore, a larger CHIP clone size was associated with lower CD4 nadir and with increased risk of MACE.\n\nIn PWH in the REPRIEVE trial who were low-to-moderate risk for incident cardiovascular disease, CHIP was not associated with increased prospective risk of MACE. However, a large CHIP was associated with increased risk of myocardial infarction and revascularization.\n\nURL: https://www.clinicaltrials.gov; Unique identifier: NCT02344290.", "doi": "10.1161/ATVBAHA.125.322896", "pmid": "41195533", "labels": {"DDLS Fellow": "", "Abhishek Niroula": ""}, "xrefs": [{"db": "mid", "key": "NIHMS2126370"}, {"db": "pmc", "key": "PMC12765570"}, {"db": "ClinicalTrials.gov", "key": "NCT02344290"}], "notes": [], "created": "2025-11-17T15:51:17.831Z", "modified": "2026-10-01T08:29:17.420Z"}, {"entity": "publication", "iuid": "cad35a21593644b9852021cda586dd3e", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/cad35a21593644b9852021cda586dd3e.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/cad35a21593644b9852021cda586dd3e"}}, "title": "Genetic modification of inflammation- and clonal hematopoiesis-associated cardiovascular risk.", "authors": [{"family": "Yu", "given": "Zhi", "initials": "Z", "orcid": "0000-0003-4810-3474", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/b4b810efe02244148b701c1468543ea3.json"}}, {"family": "Fidler", "given": "Trevor P", "initials": "TP"}, {"family": "Ruan", "given": "Yunfeng", "initials": "Y", "orcid": "0000-0002-3213-8309", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/13398a8656e64d88b858b22f59eeeb48.json"}}, {"family": "Vlasschaert", "given": "Caitlyn", "initials": "C"}, {"family": "Nakao", "given": "Tetsushi", "initials": "T", "orcid": "0000-0001-9979-2682", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/7e818cd4544c41c2a7fa91dbce13429e.json"}}, {"family": "Uddin", "given": "Md Mesbah", "initials": "MM", "orcid": "0000-0003-1846-0411", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/42f1ac7010c34ba997a3fd9e56c6a56a.json"}}, {"family": "Mack", "given": "Taralynn", "initials": "T", "orcid": "0000-0003-1043-2950", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/b126c40c737b4b06a8702801ee227b04.json"}}, {"family": "Niroula", "given": "Abhishek", "initials": "A", "orcid": "0000-0002-5904-0635", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/05df7afc7a494ba5af8a378e5ffa53f0.json"}}, {"family": "Heimlich", "given": "J Brett", "initials": "JB", "orcid": "0000-0003-2812-5326", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/57e0bced1405484b94ce062052f498c0.json"}}, {"family": "Zekavat", "given": "Seyedeh M", "initials": "SM", "orcid": "0000-0003-4026-8944", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/6234b31f08e442a9b71a711ec7b1147a.json"}}, {"family": "Gibson", "given": "Christopher J", "initials": "CJ", "orcid": "0000-0002-3700-5310", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/71ce9f64755e483496f8c28a76a2a1ff.json"}}, {"family": "Griffin", "given": "Gabriel K", "initials": "GK"}, {"family": "Wang", "given": "Yuxuan", "initials": "Y"}, {"family": "Peloso", "given": "Gina M", "initials": "GM", "orcid": "0000-0002-5355-8636", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/b1478b88eafd41d09194cf8967e8ea5f.json"}}, {"family": "Heard-Costa", "given": "Nancy", "initials": "N"}, {"family": "Levy", "given": "Daniel", "initials": "D", "orcid": "0000-0003-1843-8724", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/57605ba755d44792ab87cf14114ec757.json"}}, {"family": "Vasan", "given": "Ramachandran S", "initials": "RS", "orcid": "0000-0001-7357-5970", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/22de41f77ce541d09a9b04aa59de33f7.json"}}, {"family": "Aguet", "given": "Fran\u00e7ois", "initials": "F"}, {"family": "Ardlie", "given": "Kristin G", "initials": "KG"}, {"family": "Taylor", "given": "Kent D", "initials": "KD"}, {"family": "Rich", "given": "Stephen S", "initials": "SS", "orcid": "0000-0003-3872-7793", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/b55061262f4541c1b28d3081e4001833.json"}}, {"family": "Rotter", "given": "Jerome I", "initials": "JI", "orcid": "0000-0001-7191-1723", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/50edc25b80cc48b699db367e372fded5.json"}}, {"family": "Libby", "given": "Peter", "initials": "P", "orcid": "0000-0002-1502-502X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/39fb20acff0442bd92fc7931d3ee6cf9.json"}}, {"family": "Jaiswal", "given": "Siddhartha", "initials": "S", "orcid": "0000-0002-9597-0477", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/a1901e08f989434fb01dfa17b0a85470.json"}}, {"family": "Ebert", "given": "Benjamin L", "initials": "BL", "orcid": "0000-0003-0197-5451", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/56e4f1c53a4348e2b0ceb44a38850a17.json"}}, {"family": "Bick", "given": "Alexander G", "initials": "AG", "orcid": "0000-0001-5824-9595", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/d2da5a35a4984921b19dfafe64cea2de.json"}}, {"family": "Tall", "given": "Alan R", "initials": "AR"}, {"family": "Natarajan", "given": "Pradeep", "initials": "P", "orcid": "0000-0001-8402-7435", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/fe8bd48c61c047cd8e61c35d9e9ac650.json"}}], "type": "journal article", "published": "2023-09-15", "journal": {"title": "J. Clin. Invest.", "issn": "1558-8238", "volume": "133", "issue": "18", "issn-l": "0021-9738"}, "abstract": "Clonal hematopoiesis of indeterminate potential (CHIP) is associated with an increased risk of cardiovascular diseases (CVDs), putatively via inflammasome activation. We pursued an inflammatory gene modifier scan for CHIP-associated CVD risk among 424,651 UK Biobank participants. We identified CHIP using whole-exome sequencing data of blood DNA and modeled as a composite, considering all driver genes together, as well as separately for common drivers (DNMT3A, TET2, ASXL1, and JAK2). We developed predicted gene expression scores for 26 inflammasome-related genes and assessed how they modify CHIP-associated CVD risk. We identified IL1RAP as a potential key molecule for CHIP-associated CVD risk across genes and increased AIM2 gene expression leading to heightened JAK2- and ASXL1-associated CVD risk. We show that CRISPR-induced Asxl1-mutated murine macrophages had a particularly heightened inflammatory response to AIM2 agonism, associated with an increased DNA damage response, as well as increased IL-10 secretion, mirroring a CVD-protective effect of IL10 expression in ASXL1 CHIP. Our study supports the role of inflammasomes in CHIP-associated CVD and provides evidence to support gene-specific strategies to address CHIP-associated CVD risk.", "doi": "10.1172/JCI168597", "pmid": "37498674", "labels": {"Abhishek Niroula": null, "DDLS Fellow": null}, "xrefs": [{"db": "pmc", "key": "PMC10503804"}, {"db": "pii", "key": "168597"}], "notes": [], "created": "2023-11-20T11:39:39.730Z", "modified": "2025-04-11T07:26:34.477Z"}, {"entity": "publication", "iuid": "520bd20cb8d0415eb98887ce8e395d07", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/520bd20cb8d0415eb98887ce8e395d07.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/520bd20cb8d0415eb98887ce8e395d07"}}, "title": "Genetics of smoking and risk of clonal hematopoiesis.", "authors": [{"family": "Levin", "given": "Michael G", "initials": "MG", "orcid": "0000-0002-9937-9932", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/ed963b203f1b41ac94c167cdc2767468.json"}}, {"family": "Nakao", "given": "Tetsushi", "initials": "T", "orcid": "0000-0001-9979-2682", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/7e818cd4544c41c2a7fa91dbce13429e.json"}}, {"family": "Zekavat", "given": "Seyedeh M", "initials": "SM", "orcid": "0000-0003-4026-8944", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/6234b31f08e442a9b71a711ec7b1147a.json"}}, {"family": "Koyama", "given": "Satoshi", "initials": "S", "orcid": "0000-0002-9286-0360", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/8e79637c05b54d7089b1d23155db2b3a.json"}}, {"family": "Bick", "given": "Alexander G", "initials": "AG", "orcid": "0000-0001-5824-9595", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/d2da5a35a4984921b19dfafe64cea2de.json"}}, {"family": "Niroula", "given": "Abhishek", "initials": "A"}, {"family": "Ebert", "given": "Benjamin", "initials": "B"}, {"family": "Damrauer", "given": "Scott M", "initials": "SM", "orcid": "0000-0001-8009-1632", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/f35b78d4384d41f2bfae2639b23b1e82.json"}}, {"family": "Natarajan", "given": "Pradeep", "initials": "P", "orcid": "0000-0001-8402-7435", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/fe8bd48c61c047cd8e61c35d9e9ac650.json"}}], "type": "journal article", "published": "2022-05-04", "journal": {"title": "Sci Rep", "issn": "2045-2322", "volume": "12", "issue": "1", "pages": "7248", "issn-l": "2045-2322"}, "abstract": "Clonal hematopoiesis of indeterminate potential (CHIP) and mosaic chromosomal alterations (mCAs) represent two forms of clonal hematopoiesis where clones bearing expanded somatic mutations have been linked to both oncologic and non-oncologic clinical outcomes including atherosclerosis and all-cause mortality. Epidemiologic studies have highlighted smoking as an important driver of somatic mutations across multiple tissues. However, establishing the causal role of smoking in clonal hematopoiesis has been limited by observational study designs, which may suffer from confounding and reverse-causality. We performed two complementary analyses to investigate the role of smoking in mCAs and CHIP. First, using an observational study design among UK Biobank participants, we confirmed strong associations between smoking and mCAs. Second, using two-sample Mendelian randomization, smoking was strongly associated with mCA but not with CHIP. Overall, these results support a causal association between smoking and mCAs and suggest smoking may variably shape the fitness of clones bearing somatic mutations.", "doi": "10.1038/s41598-022-09604-z", "pmid": "35508625", "labels": {"Abhishek Niroula": null, "DDLS Fellow": null}, "xrefs": [{"db": "pmc", "key": "PMC9068754"}, {"db": "pii", "key": "10.1038/s41598-022-09604-z"}], "notes": [], "created": "2023-11-20T11:36:19.186Z", "modified": "2023-11-20T11:36:19.393Z"}, {"entity": "publication", "iuid": "5a4b7afcc7f14c88b78aa139fc346ea0", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/5a4b7afcc7f14c88b78aa139fc346ea0.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/5a4b7afcc7f14c88b78aa139fc346ea0"}}, "title": "Mendelian randomization supports bidirectional causality between telomere length and clonal hematopoiesis of indeterminate potential.", "authors": [{"family": "Nakao", "given": "Tetsushi", "initials": 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"https://publications-affiliated.scilifelab.se/researcher/39fb20acff0442bd92fc7931d3ee6cf9.json"}}, {"family": "Ellinor", "given": "Patrick T", "initials": "PT", "orcid": "0000-0002-2067-0533", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/fd1830794e884e6e849fd4f7645c9b61.json"}}, {"family": "Pankratz", "given": "Nathan", "initials": "N", "orcid": "0000-0001-5958-693X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/ad5e6b749b264d1e83ea58d5bce6c88e.json"}}, {"family": "Ebert", "given": "Benjamin L", "initials": "BL", "orcid": "0000-0003-0197-5451", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/56e4f1c53a4348e2b0ceb44a38850a17.json"}}, {"family": "Reiner", "given": "Alexander P", "initials": "AP"}, {"family": "Mathias", "given": "Rasika A", "initials": "RA", "orcid": "0000-0002-2282-9042", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/71dfe469451f4573bcccc96f981f7915.json"}}, {"family": "Do", "given": "Ron", "initials": "R", "orcid": "0000-0002-3144-3627", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/4ab0c452994042219ca6120d45e72604.json"}}, {"family": "NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium", "given": "", "initials": ""}, {"family": "Natarajan", "given": "Pradeep", "initials": "P", "orcid": "0000-0001-8402-7435", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/fe8bd48c61c047cd8e61c35d9e9ac650.json"}}], "type": "journal article", "published": "2022-04-08", "journal": {"title": "Sci Adv", "issn": "2375-2548", "volume": "8", "issue": "14", "pages": "eabl6579", "issn-l": "2375-2548"}, "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.", "doi": "10.1126/sciadv.abl6579", "pmid": "35385311", "labels": {"Abhishek Niroula": null, "DDLS Fellow": null}, "xrefs": [{"db": "pmc", "key": "PMC8986098"}], "notes": [], "created": "2023-11-20T11:36:14.966Z", "modified": "2023-11-20T11:36:17.765Z"}]}