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dc.contributor.authorNakao, Tetsushi
dc.contributor.authorBick, Alexander G
dc.contributor.authorTaub, Margaret A
dc.contributor.authorZekavat, Seyedeh M
dc.contributor.authorUddin, Md M
dc.contributor.authorNiroula, Abhishek
dc.contributor.authorCarty, Cara L
dc.contributor.authorLane, John
dc.contributor.authorHonigberg, Michael C
dc.contributor.authorWeinstock, Joshua S
dc.contributor.authorPampana, Akhil
dc.contributor.authorGibson, Christopher J
dc.contributor.authorGriffin, Gabriel K
dc.contributor.authorClarke, Shoa L
dc.contributor.authorBhattacharya, Romit
dc.contributor.authorAssimes, Themistocles L
dc.contributor.authorEmery, Leslie S
dc.contributor.authorStilp, Adrienne M
dc.contributor.authorWong, Quenna
dc.contributor.authorBroome, Jai
dc.contributor.authorLaurie, Cecelia A
dc.contributor.authorKhan, Alyna T
dc.contributor.authorSmith, Albert V
dc.contributor.authorBlackwell, Thomas W
dc.contributor.authorCodd, Veryan
dc.contributor.authorNelson, Christopher P
dc.contributor.authorYoneda, Zachary T
dc.contributor.authorPeralta, Juan M
dc.contributor.authorBowden, Donald W
dc.contributor.authorIrvin, Marguerite R
dc.contributor.authorBoorgula, Meher
dc.contributor.authorZhao, Wei
dc.contributor.authorYanek, Lisa R
dc.contributor.authorWiggins, Kerri L
dc.contributor.authorHixson, James E
dc.contributor.authorGu, C Charles
dc.contributor.authorPeloso, Gina M
dc.contributor.authorRoden, Dan M
dc.contributor.authorReupena, Muagututi'a S
dc.contributor.authorHwu, Chii-Min
dc.contributor.authorDeMeo, Dawn L
dc.contributor.authorNorth, Kari E
dc.contributor.authorKelly, Shannon
dc.contributor.authorMusani, Solomon K
dc.contributor.authorBis, Joshua C
dc.contributor.authorLloyd-Jones, Donald M
dc.contributor.authorJohnsen, Jill M
dc.contributor.authorPreuss, Michael
dc.contributor.authorTracy, Russell P
dc.contributor.authorPeyser, Patricia A
dc.contributor.authorQiao, Dandi
dc.contributor.authorDesai, Pinkal
dc.contributor.authorCurran, Joanne E
dc.contributor.authorFreedman, Barry I
dc.contributor.authorTiwari, Hemant K
dc.contributor.authorChavan, Sameer
dc.contributor.authorSmith, Jennifer A
dc.contributor.authorSmith, Nicholas L
dc.contributor.authorKelly, Tanika N
dc.contributor.authorHidalgo, Bertha
dc.contributor.authorCupples, L Adrienne
dc.contributor.authorWeeks, Daniel E
dc.contributor.authorHawley, Nicola L
dc.contributor.authorMinster, Ryan L
dc.contributor.authorSamoan Obesity, Lifestyle and Genetic Adaptations Study (OLaGA) Group
dc.contributor.authorDeka, Ranjan
dc.contributor.authorNaseri, Take T
dc.contributor.authorde Las Fuentes, Lisa
dc.contributor.authorRaffield, Laura M
dc.contributor.authorMorrison, Alanna C
dc.contributor.authorVries, Paul S
dc.contributor.authorBallantyne, Christie M
dc.contributor.authorKenny, Eimear E
dc.contributor.authorRich, Stephen S
dc.contributor.authorWhitsel, Eric A
dc.contributor.authorCho, Michael H
dc.contributor.authorShoemaker, M Benjamin
dc.contributor.authorPace, Betty S
dc.contributor.authorBlangero, John
dc.contributor.authorPalmer, Nicholette D
dc.contributor.authorMitchell, Braxton D
dc.contributor.authorShuldiner, Alan R
dc.contributor.authorBarnes, Kathleen C
dc.contributor.authorRedline, Susan
dc.contributor.authorKardia, Sharon LR
dc.contributor.authorAbecasis, Gonçalo R
dc.contributor.authorBecker, Lewis C
dc.contributor.authorHeckbert, Susan R
dc.contributor.authorHe, Jiang
dc.contributor.authorPost, Wendy
dc.contributor.authorArnett, Donna K
dc.contributor.authorVasan, Ramachandran S
dc.contributor.authorDarbar, Dawood
dc.contributor.authorWeiss, Scott T
dc.contributor.authorMcGarvey, Stephen T
dc.contributor.authorde Andrade, Mariza
dc.contributor.authorChen, Yii-Der Ida
dc.contributor.authorKaplan, Robert C
dc.contributor.authorMeyers, Deborah A
dc.contributor.authorCuster, Brian S
dc.contributor.authorCorrea, Adolfo
dc.contributor.authorPsaty, Bruce M
dc.contributor.authorFornage, Myriam
dc.contributor.authorManson, JoAnn E
dc.contributor.authorBoerwinkle, Eric
dc.contributor.authorKonkle, Barbara A
dc.contributor.authorLoos, Ruth JF
dc.contributor.authorRotter, Jerome I
dc.contributor.authorSilverman, Edwin K
dc.contributor.authorKooperberg, Charles
dc.contributor.authorDanesh, John
dc.contributor.authorSamani, Nilesh J
dc.contributor.authorJaiswal, Siddhartha
dc.contributor.authorLibby, Peter
dc.contributor.authorEllinor, Patrick T
dc.contributor.authorPankratz, Nathan
dc.contributor.authorEbert, Benjamin L
dc.contributor.authorReiner, Alexander P
dc.contributor.authorMathias, Rasika A
dc.contributor.authorDo, Ron
dc.contributor.authorNHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium
dc.contributor.authorNatarajan, Pradeep
dc.date.accessioned2022-05-09T11:05:28Z
dc.date.available2022-05-09T11:05:28Z
dc.date.issued2022-04-08
dc.identifier.issn2375-2548
dc.identifier.other35385311
dc.identifier.otherPMC8986098
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/336929
dc.description.abstractHuman 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.
dc.languageeng
dc.publisherAmerican Association for the Advancement of Science (AAAS)
dc.rightsAttribution-NonCommercial 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by-nc/4.0/
dc.sourcenlmid: 101653440
dc.sourceessn: 2375-2548
dc.titleMendelian randomization supports bidirectional causality between telomere length and clonal hematopoiesis of indeterminate potential.
dc.typeArticle
dc.date.updated2022-05-09T11:05:27Z
prism.issueIdentifier14
prism.publicationNameSci Adv
prism.volume8
dc.identifier.doi10.17863/CAM.84348
dcterms.dateAccepted2022-02-16
rioxxterms.versionofrecord10.1126/sciadv.abl6579
rioxxterms.versionVoR
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by-nc/4.0/
dc.contributor.orcidNakao, Tetsushi [0000-0001-9979-2682]
dc.contributor.orcidBick, Alexander G [0000-0001-5824-9595]
dc.contributor.orcidZekavat, Seyedeh M [0000-0003-4026-8944]
dc.contributor.orcidUddin, Md M [0000-0003-1846-0411]
dc.contributor.orcidNiroula, Abhishek [0000-0002-5904-0635]
dc.contributor.orcidCarty, Cara L [0000-0002-6378-8195]
dc.contributor.orcidLane, John [0000-0002-3582-5825]
dc.contributor.orcidHonigberg, Michael C [0000-0001-8630-5021]
dc.contributor.orcidWeinstock, Joshua S [0000-0001-7013-1899]
dc.contributor.orcidPampana, Akhil [0000-0002-4167-0540]
dc.contributor.orcidGriffin, Gabriel K [0000-0002-4042-6757]
dc.contributor.orcidClarke, Shoa L [0000-0002-6592-1172]
dc.contributor.orcidBhattacharya, Romit [0000-0002-0782-4753]
dc.contributor.orcidAssimes, Themistocles L [0000-0003-2349-0009]
dc.contributor.orcidEmery, Leslie S [0000-0002-9070-9886]
dc.contributor.orcidStilp, Adrienne M [0000-0002-3910-0776]
dc.contributor.orcidWong, Quenna [0000-0002-9027-2100]
dc.contributor.orcidBroome, Jai [0000-0001-7638-0749]
dc.contributor.orcidKhan, Alyna T [0000-0002-2240-7931]
dc.contributor.orcidSmith, Albert V [0000-0003-1942-5845]
dc.contributor.orcidCodd, Veryan [0000-0002-9430-8254]
dc.contributor.orcidNelson, Christopher P [0000-0001-8025-2897]
dc.contributor.orcidYoneda, Zachary T [0000-0002-2055-732X]
dc.contributor.orcidPeralta, Juan M [0000-0002-8811-5579]
dc.contributor.orcidYanek, Lisa R [0000-0001-7117-1075]
dc.contributor.orcidWiggins, Kerri L [0000-0003-2749-1279]
dc.contributor.orcidGu, C Charles [0000-0002-8527-8145]
dc.contributor.orcidPeloso, Gina M [0000-0002-5355-8636]
dc.contributor.orcidRoden, Dan M [0000-0002-6302-0389]
dc.contributor.orcidHwu, Chii-Min [0000-0002-8209-9627]
dc.contributor.orcidNorth, Kari E [0000-0002-8903-0366]
dc.contributor.orcidBis, Joshua C [0000-0002-3409-1110]
dc.contributor.orcidLloyd-Jones, Donald M [0000-0003-0847-6110]
dc.contributor.orcidJohnsen, Jill M [0000-0002-2279-2550]
dc.contributor.orcidPreuss, Michael [0000-0001-5266-8465]
dc.contributor.orcidTracy, Russell P [0000-0002-0080-2420]
dc.contributor.orcidPeyser, Patricia A [0000-0002-9717-8459]
dc.contributor.orcidQiao, Dandi [0000-0001-9450-205X]
dc.contributor.orcidCurran, Joanne E [0000-0002-6898-155X]
dc.contributor.orcidFreedman, Barry I [0000-0003-0275-5530]
dc.contributor.orcidChavan, Sameer [0000-0002-0220-0845]
dc.contributor.orcidSmith, Jennifer A [0000-0002-3575-5468]
dc.contributor.orcidKelly, Tanika N [0000-0002-7348-4451]
dc.contributor.orcidHidalgo, Bertha [0000-0002-2556-1969]
dc.contributor.orcidWeeks, Daniel E [0000-0001-9410-7228]
dc.contributor.orcidHawley, Nicola L [0000-0002-2601-3454]
dc.contributor.orcidMinster, Ryan L [0000-0001-7382-6717]
dc.contributor.orcidde Las Fuentes, Lisa [0000-0002-4689-325X]
dc.contributor.orcidRaffield, Laura M [0000-0002-7892-193X]
dc.contributor.orcidBallantyne, Christie M [0000-0002-6432-1730]
dc.contributor.orcidKenny, Eimear E [0000-0001-9198-759X]
dc.contributor.orcidRich, Stephen S [0000-0003-3872-7793]
dc.contributor.orcidWhitsel, Eric A [0000-0003-4843-3641]
dc.contributor.orcidCho, Michael H [0000-0002-4907-1657]
dc.contributor.orcidPalmer, Nicholette D [0000-0001-8883-2511]
dc.contributor.orcidMitchell, Braxton D [0000-0003-4920-4744]
dc.contributor.orcidShuldiner, Alan R [0000-0001-9921-4305]
dc.contributor.orcidRedline, Susan [0000-0002-6585-1610]
dc.contributor.orcidHeckbert, Susan R [0000-0002-7100-512X]
dc.contributor.orcidHe, Jiang [0000-0002-8286-9652]
dc.contributor.orcidPost, Wendy [0000-0002-8655-5204]
dc.contributor.orcidArnett, Donna K [0000-0003-2219-657X]
dc.contributor.orcidVasan, Ramachandran S [0000-0001-7357-5970]
dc.contributor.orcidWeiss, Scott T [0000-0001-7196-303X]
dc.contributor.orcidMcGarvey, Stephen T [0000-0003-1233-6970]
dc.contributor.orcidCuster, Brian S [0000-0001-6251-366X]
dc.contributor.orcidCorrea, Adolfo [0000-0002-9501-600X]
dc.contributor.orcidManson, JoAnn E [0000-0002-9426-7595]
dc.contributor.orcidKonkle, Barbara A [0000-0002-3959-8797]
dc.contributor.orcidLoos, Ruth JF [0000-0002-8532-5087]
dc.contributor.orcidRotter, Jerome I [0000-0001-7191-1723]
dc.contributor.orcidSilverman, Edwin K [0000-0002-3641-3822]
dc.contributor.orcidKooperberg, Charles [0000-0002-7986-8560]
dc.contributor.orcidDanesh, John [0000-0003-1158-6791]
dc.contributor.orcidSamani, Nilesh J [0000-0002-3286-8133]
dc.contributor.orcidJaiswal, Siddhartha [0000-0002-9597-0477]
dc.contributor.orcidLibby, Peter [0000-0002-1502-502X]
dc.contributor.orcidEllinor, Patrick T [0000-0002-2067-0533]
dc.contributor.orcidPankratz, Nathan [0000-0001-5958-693X]
dc.contributor.orcidEbert, Benjamin L [0000-0003-0197-5451]
dc.contributor.orcidMathias, Rasika A [0000-0002-2282-9042]
dc.contributor.orcidDo, Ron [0000-0002-3144-3627]
dc.contributor.orcidNatarajan, Pradeep [0000-0001-8402-7435]
dc.identifier.eissn2375-2548
pubs.funder-project-idMedical Research Council (MR/M012816/1)
cam.issuedOnline2022-04-06


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Attribution-NonCommercial 4.0 International
Except where otherwise noted, this item's licence is described as Attribution-NonCommercial 4.0 International