Contribution of genetics to hematopoietic stem cell mobilization : a genome-wide association study of 564 healthy donors mobilized with granulocyte colony-stimulating factor
(2025) In Haematologica 110(11). p.2683-2690- Abstract
Hematopoietic stem and progenitor cells (HSPC) from mobilized blood are the preferred graft source for allogeneic and autologous stem cell transplantation. The efficiency of CD34+ cell mobilization with granulocyte colony-stimulating factor (G-CSF) varies significantly between individuals, but is reproducible across mobilization cycles within an individual, suggesting a genetic component, a hypothesis that has been previously investigated by testing for candidate single-nucleotide polymorphisms (SNP) associations. As the genetic determinants of HSPC mobilization have not been analyzed on the genomic scale so far, we performed a genome-wide association study (GWAS) in a German population of 564 healthy G-CSF mobilized allogeneic stem... (More)
Hematopoietic stem and progenitor cells (HSPC) from mobilized blood are the preferred graft source for allogeneic and autologous stem cell transplantation. The efficiency of CD34+ cell mobilization with granulocyte colony-stimulating factor (G-CSF) varies significantly between individuals, but is reproducible across mobilization cycles within an individual, suggesting a genetic component, a hypothesis that has been previously investigated by testing for candidate single-nucleotide polymorphisms (SNP) associations. As the genetic determinants of HSPC mobilization have not been analyzed on the genomic scale so far, we performed a genome-wide association study (GWAS) in a German population of 564 healthy G-CSF mobilized allogeneic stem cell donors. None of the association between about 5 million variants and the primary outcome investigated (CD34+ cell frequency in peripheral blood) reached genome-wide significance. Focused analysis of 11 variants previously shown to be associated with basal CD34+ cell levels confirmed an association of CXCR4-rs11688530 (A>G) and ARHGAP45-rs36084354 (A>G) with higher CD34+ frequency in G-CSF mobilized healthy donors showing an explained variance (Varex) of 1.07% (P=0.004) and 0.86% (P=0.01), respectively. Demographic analysis revealed an association of peripheral blood CD34+ cell frequency with sex (Varex=8.1%) and body mass index (Varex=7.2%) that exceeded the contribution of single variants. The current study is the first GWAS in mobilized stem cell donors and had a statistical power of 80% to detect single nucleotide polymorphism with Varex of ≥6.7% at genome-wide significance. The study results exclude a monogenetic cause of population G-CSF responsiveness and support the view that polygenetic risk scores are required as predictors.
(Less)
- author
- organization
- publishing date
- 2025-11-01
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Haematologica
- volume
- 110
- issue
- 11
- pages
- 8 pages
- publisher
- Ferrata Storti Foundation
- external identifiers
-
- pmid:40468967
- scopus:105020776973
- ISSN
- 1592-8721
- DOI
- 10.3324/haematol.2025.287637
- language
- English
- LU publication?
- yes
- id
- e1c94747-5b91-434d-af00-abe102c5a5ed
- date added to LUP
- 2025-12-15 13:38:24
- date last changed
- 2025-12-16 03:00:15
@article{e1c94747-5b91-434d-af00-abe102c5a5ed,
abstract = {{<p>Hematopoietic stem and progenitor cells (HSPC) from mobilized blood are the preferred graft source for allogeneic and autologous stem cell transplantation. The efficiency of CD34+ cell mobilization with granulocyte colony-stimulating factor (G-CSF) varies significantly between individuals, but is reproducible across mobilization cycles within an individual, suggesting a genetic component, a hypothesis that has been previously investigated by testing for candidate single-nucleotide polymorphisms (SNP) associations. As the genetic determinants of HSPC mobilization have not been analyzed on the genomic scale so far, we performed a genome-wide association study (GWAS) in a German population of 564 healthy G-CSF mobilized allogeneic stem cell donors. None of the association between about 5 million variants and the primary outcome investigated (CD34+ cell frequency in peripheral blood) reached genome-wide significance. Focused analysis of 11 variants previously shown to be associated with basal CD34+ cell levels confirmed an association of CXCR4-rs11688530 (A>G) and ARHGAP45-rs36084354 (A>G) with higher CD34+ frequency in G-CSF mobilized healthy donors showing an explained variance (Varex) of 1.07% (P=0.004) and 0.86% (P=0.01), respectively. Demographic analysis revealed an association of peripheral blood CD34+ cell frequency with sex (Varex=8.1%) and body mass index (Varex=7.2%) that exceeded the contribution of single variants. The current study is the first GWAS in mobilized stem cell donors and had a statistical power of 80% to detect single nucleotide polymorphism with Varex of ≥6.7% at genome-wide significance. The study results exclude a monogenetic cause of population G-CSF responsiveness and support the view that polygenetic risk scores are required as predictors.</p>}},
author = {{Stenzinger, Miriam and Beck, Susanne and Ourailidis, Iordanis and Volckmar, Anna Lena and Paramasivam, Nagarajan and Ahadova, Aysel and Portilla, Aitzkoa Lopez de Lapuente and La Yen, Phuong and Nilsson, Bjorn and Bermejo, Justo Lorenzo and Bonig, Halvard and Budczies, Jan}},
issn = {{1592-8721}},
language = {{eng}},
month = {{11}},
number = {{11}},
pages = {{2683--2690}},
publisher = {{Ferrata Storti Foundation}},
series = {{Haematologica}},
title = {{Contribution of genetics to hematopoietic stem cell mobilization : a genome-wide association study of 564 healthy donors mobilized with granulocyte colony-stimulating factor}},
url = {{http://dx.doi.org/10.3324/haematol.2025.287637}},
doi = {{10.3324/haematol.2025.287637}},
volume = {{110}},
year = {{2025}},
}