{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Kar SP"],"funding":["Cancer Research UK","British Heart Foundation","Medical Research Council","Blood Cancer UK","National Institute for Health Research (NIHR)","Ministry of Economy and Competitiveness | Instituto de Salud Carlos III","Wellcome Trust","Research Councils UK","Leukemia and Lymphoma Society"],"pagination":["1155-1166"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9355874"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["54(8)"],"pubmed_abstract":["Clonal hematopoiesis (CH), the clonal expansion of a blood stem cell and its progeny driven by somatic driver mutations, affects over a third of people, yet remains poorly understood. Here we analyze genetic data from 200,453 UK Biobank participants to map the landscape of inherited predisposition to CH, increasing the number of germline associations with CH in European-ancestry populations from 4 to 14. Genes at new loci implicate DNA damage repair (PARP1, ATM, CHEK2), hematopoietic stem cell migration/homing (CD164) and myeloid oncogenesis (SETBP1). Several associations were CH-subtype-specific including variants at TCL1A and CD164 that had opposite associations with DNMT3A- versus TET2-mutant CH, the two most common CH subtypes, proposing key roles for these two loci in CH development. "],"journal":["Nature genetics"],"pubmed_title":["Genome-wide analyses of 200,453 individuals yield new insights into the causes and consequences of clonal hematopoiesis."],"pmcid":["PMC9355874"],"funding_grant_id":["MC_PC_17228","C22324/A23015","Miguel Servet Program (CP20/00130)","MC_PC_17230","29019","RG/18/13/33946","MR/T043202/1","204623/Z/16/Z","23015","HDR-9004","WT098051","204623","BRC-1215-20014","A23015","RTF6006-19","RG/13/13/30194","A29019","C18281/A29019","CH/12/2/29428","MC_UU_00002/7","098051","MC_QA137853"],"pubmed_authors":["Mitchell J","Barcena C","Fabre MA","Kar SP","Vassiliou GS","Jiang T","Burgess S","Langdon R","Vijayabaskar MS","Quiros PM","Carter P","Gu M","Iyer V","Petrovski S"],"additional_accession":[]},"is_claimable":false,"name":"Genome-wide analyses of 200,453 individuals yield new insights into the causes and consequences of clonal hematopoiesis.","description":"Clonal hematopoiesis (CH), the clonal expansion of a blood stem cell and its progeny driven by somatic driver mutations, affects over a third of people, yet remains poorly understood. Here we analyze genetic data from 200,453 UK Biobank participants to map the landscape of inherited predisposition to CH, increasing the number of germline associations with CH in European-ancestry populations from 4 to 14. Genes at new loci implicate DNA damage repair (PARP1, ATM, CHEK2), hematopoietic stem cell migration/homing (CD164) and myeloid oncogenesis (SETBP1). Several associations were CH-subtype-specific including variants at TCL1A and CD164 that had opposite associations with DNMT3A- versus TET2-mutant CH, the two most common CH subtypes, proposing key roles for these two loci in CH development. ","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Aug","modification":"2026-05-09T14:11:22.654Z","creation":"2024-11-19T22:29:21.417Z"},"accession":"S-EPMC9355874","cross_references":{"pubmed":["35835912"],"doi":["10.1038/s41588-022-01121-z"]}}