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dc.contributor.authorZink, Florian
dc.contributor.authorStacey, Simon N
dc.contributor.authorNorddahl, Gudmundur L
dc.contributor.authorFrigge, Michael L
dc.contributor.authorMagnusson, Olafur T
dc.contributor.authorJonsdottir, Ingileif
dc.contributor.authorThorgeirsson, Thorgeir E
dc.contributor.authorSigurdsson, Asgeir
dc.contributor.authorGudjonsson, Sigurjon A
dc.contributor.authorGudmundsson, Julius
dc.contributor.authorJonasson, Jon G
dc.contributor.authorTryggvadottir, Laufey
dc.contributor.authorJonsson, Thorvaldur
dc.contributor.authorHelgason, Agnar
dc.contributor.authorGylfason, Arnaldur
dc.contributor.authorSulem, Patrick
dc.contributor.authorRafnar, Thorunn
dc.contributor.authorThorsteinsdottir, Unnur
dc.contributor.authorGudbjartsson, Daniel F
dc.contributor.authorMasson, Gisli
dc.contributor.authorKong, Augustine
dc.contributor.authorStefansson, Kari
dc.date.accessioned2017-09-21T13:02:03Z
dc.date.available2017-09-21T13:02:03Z
dc.date.issued2017-08-10
dc.identifier.citationClonal hematopoiesis, with and without candidate driver mutations, is common in the elderly. 2017, 130 (6):742-752 Blooden
dc.identifier.issn1528-0020
dc.identifier.pmid28483762
dc.identifier.doi10.1182/blood-2017-02-769869
dc.identifier.urihttp://hdl.handle.net/2336/620300
dc.description.abstractClonal hematopoiesis (CH) arises when a substantial proportion of mature blood cells is derived from a single dominant hematopoietic stem cell lineage. Somatic mutations in candidate driver (CD) genes are thought to be responsible for at least some cases of CH. Using whole-genome sequencing of 11 262 Icelanders, we found 1403 cases of CH by using barcodes of mosaic somatic mutations in peripheral blood, whether or not they have a mutation in a CD gene. We find that CH is very common in the elderly, trending toward inevitability. We show that somatic mutations in TET2, DNMT3A, ASXL1, and PPM1D are associated with CH at high significance. However, known CD mutations were evident in only a fraction of CH cases. Nevertheless, the highly prevalent CH we detect associates with increased mortality rates, risk for hematological malignancy, smoking behavior, telomere length, Y-chromosome loss, and other phenotypic characteristics. Modeling suggests some CH cases could arise in the absence of CD mutations as a result of neutral drift acting on a small population of active hematopoietic stem cells. Finally, we find a germline deletion in intron 3 of the telomerase reverse transcriptase (TERT) gene that predisposes to CH (rs34002450; P = 7.4 × 10(-12); odds ratio, 1.37).
dc.description.sponsorshipNational Institutes of Health, National Institute on Drug Abuseen
dc.language.isoenen
dc.publisherAmer Soc Hematologyen
dc.relation.urlhttp://www.bloodjournal.org/content/130/6/742en
dc.rightsArchived with thanks to Blooden
dc.subjectBlóðsjúkdómaren
dc.subjectAldraðiren
dc.subjectNAF12en
dc.subjectPTT12en
dc.subject.meshAdulten
dc.subject.meshAge Factorsen
dc.subject.meshAgeden
dc.subject.meshAged, 80 and overen
dc.subject.meshClone Cellsen
dc.subject.meshDNA (Cytosine-5-)-Methyltransferaseen
dc.subject.meshDNA-Binding Proteinsen
dc.subject.meshFemaleen
dc.subject.meshHematologic Neoplasmsen
dc.subject.meshHematopoiesisen
dc.subject.meshHematopoietic Stem Cellsen
dc.subject.meshHumansen
dc.subject.meshMaleen
dc.subject.meshMiddle Ageden
dc.subject.meshMutationen
dc.subject.meshProtein Phosphatase 2Cen
dc.subject.meshProto-Oncogene Proteinsen
dc.subject.meshRepressor Proteinsen
dc.subject.meshRisk Factorsen
dc.titleClonal hematopoiesis, with and without candidate driver mutations, is common in the elderly.en
dc.typeArticleen
dc.contributor.department1 deCODE genetics/AMGEN, Reykjavik, Iceland. 2 Landspitali-University Hospital, Reykjavik, Iceland. 3 Faculty of Medicine, University of Iceland, Reykjavik, Iceland. 4 Icelandic Cancer Registry, Reykjavik, Iceland; and. 5 Department of Anthropology and. 6 School of Engineering and Natural Sciences, University of Iceland, Reykjavik, Iceland.en
dc.identifier.journalBlooden
dc.rights.accessLandspitali Access - LSH-aðganguren
html.description.abstractClonal hematopoiesis (CH) arises when a substantial proportion of mature blood cells is derived from a single dominant hematopoietic stem cell lineage. Somatic mutations in candidate driver (CD) genes are thought to be responsible for at least some cases of CH. Using whole-genome sequencing of 11 262 Icelanders, we found 1403 cases of CH by using barcodes of mosaic somatic mutations in peripheral blood, whether or not they have a mutation in a CD gene. We find that CH is very common in the elderly, trending toward inevitability. We show that somatic mutations in TET2, DNMT3A, ASXL1, and PPM1D are associated with CH at high significance. However, known CD mutations were evident in only a fraction of CH cases. Nevertheless, the highly prevalent CH we detect associates with increased mortality rates, risk for hematological malignancy, smoking behavior, telomere length, Y-chromosome loss, and other phenotypic characteristics. Modeling suggests some CH cases could arise in the absence of CD mutations as a result of neutral drift acting on a small population of active hematopoietic stem cells. Finally, we find a germline deletion in intron 3 of the telomerase reverse transcriptase (TERT) gene that predisposes to CH (rs34002450; P = 7.4 × 10(-12); odds ratio, 1.37).


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