{"entity": "publication", "iuid": "a7ef7b5645ea42cea42f0f56879378a8", "timestamp": "2026-03-10T02:59:02.508Z", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/a7ef7b5645ea42cea42f0f56879378a8.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/a7ef7b5645ea42cea42f0f56879378a8"}}, "title": "Genome-wide association study on 13 167 individuals identifies regulators of blood CD34+cell levels.", "authors": [{"family": "Lopez de Lapuente Portilla", "given": "Aitzkoa", "initials": "A"}, {"family": "Ekdahl", "given": "Ludvig", "initials": "L", "orcid": "0000-0002-4257-7284", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/4a3d35910b344c849efbb73fe4a630a3.json"}}, {"family": "Cafaro", "given": "Caterina", "initials": "C"}, {"family": "Ali", "given": "Zain", "initials": "Z"}, {"family": "Miharada", "given": "Natsumi", "initials": "N"}, {"family": "Thorleifsson", "given": "Gudmar", "initials": "G"}, {"family": "\u017demaitis", "given": "Kristijonas", "initials": "K", "orcid": "0000-0002-4098-0184", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/623fb0a2c32247e4845e84f830dd18fe.json"}}, {"family": "Lamarca Arrizabalaga", "given": "Antton", "initials": "A"}, {"family": "Thodberg", "given": "Malte", "initials": "M", "orcid": "0000-0001-6244-3841", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/7f2c232400714922bdbd28e77ede971e.json"}}, {"family": "Pertesi", "given": "Maroulio", "initials": "M"}, {"family": "Dhapola", "given": "Parashar", "initials": "P", "orcid": "0000-0002-8070-7238", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/e18a6fdfca924c549d5b20c79111867c.json"}}, {"family": "Bao", "given": "Erik", "initials": "E"}, {"family": "Niroula", "given": "Abhishek", "initials": "A"}, {"family": "Bali", "given": "Divya", "initials": "D", "orcid": "0000-0003-3178-1586", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/bbcd91ef892d4eeca466eed9adf596f7.json"}}, {"family": "Norddahl", "given": "Gudmundur", "initials": "G"}, {"family": "Ugidos Damboriena", "given": "Nerea", "initials": "N", "orcid": "0000-0003-4938-3973", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/8deff5e6dcb64aa1b6f24292cde28d03.json"}}, {"family": "Sankaran", "given": "Vijay G", "initials": "VG", "orcid": "0000-0003-0044-443X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/0a967a5a378f406299b3fefe244361c9.json"}}, {"family": "Karlsson", "given": "G\u00f6ran", "initials": "G"}, {"family": "Thorsteinsdottir", "given": "Unnur", "initials": "U"}, {"family": "Larsson", "given": "Jonas", "initials": "J"}, {"family": "Stefansson", "given": "Kari", "initials": "K"}, {"family": "Nilsson", "given": "Bj\u00f6rn", "initials": "B"}], "type": "journal article", "published": "2022-03-17", "journal": {"title": "Blood", "issn": "1528-0020", "volume": "139", "issue": "11", "pages": "1659-1669", "issn-l": "0006-4971"}, "abstract": "Stem cell transplantation is a cornerstone in the treatment of blood malignancies. The most common method to harvest stem cells for transplantation is by leukapheresis, requiring mobilization of CD34+ hematopoietic stem and progenitor cells (HSPCs) from the bone marrow into the blood. Identifying the genetic factors that control blood CD34+ cell levels could reveal new drug targets for HSPC mobilization. Here we report the first large-scale, genome-wide association study on blood CD34+ cell levels. Across 13 167 individuals, we identify 9 significant and 2 suggestive associations, accounted for by 8 loci (PPM1H, CXCR4, ENO1-RERE, ITGA9, ARHGAP45, CEBPA, TERT, and MYC). Notably, 4 of the identified associations map to CXCR4, showing that bona fide regulators of blood CD34+ cell levels can be identified through genetic variation. Further, the most significant association maps to PPM1H, encoding a serine/threonine phosphatase never previously implicated in HSPC biology. PPM1H is expressed in HSPCs, and the allele that confers higher blood CD34+ cell levels downregulates PPM1H. Through functional fine-mapping, we find that this downregulation is caused by the variant rs772557-A, which abrogates an MYB transcription factor-binding site in PPM1H intron 1 that is active in specific HSPC subpopulations, including hematopoietic stem cells, and interacts with the promoter by chromatin looping. Furthermore, PPM1H knockdown increases the proportion of CD34+ and CD34+90+ cells in cord blood assays. Our results provide the first large-scale analysis of the genetic architecture of blood CD34+ cell levels and warrant further investigation of PPM1H as a potential inhibition target for stem cell mobilization.", "doi": "10.1182/blood.2021013220", "pmid": "35007327", "labels": {"Abhishek Niroula": null, "DDLS Fellow": null}, "xrefs": [{"db": "pii", "key": "S0006-4971(22)00038-6"}], "notes": [], "created": "2023-11-20T11:36:11.310Z", "modified": "2023-11-20T11:36:11.572Z"}