A genome-wide association study on hematopoietic stem cell transplantation reveals novel genomic loci associated with transplant outcomes

Albert Rosenberger; Rachel E Crossland; Ralf Dressel; Dieter Kube; Daniel Wolff; Gerald Wulf; Heike Bickeböller; Anne Dickinson; Ernst Holler

doi:10.3389/fimmu.2024.1280876

A genome-wide association study on hematopoietic stem cell transplantation reveals novel genomic loci associated with transplant outcomes

Front Immunol. 2024 Feb 7:15:1280876. doi: 10.3389/fimmu.2024.1280876. eCollection 2024.

Authors

Affiliations

¹ Department of Genetic Epidemiology, University Medical Center, Georg August University Göttingen, Göttingen, Germany.
² Translational & Clinical Research Institute, Faculty of Medical Science, Medical School, Newcastle University, Newcastle upon Tyne, United Kingdom.
³ Department of Cellular and Molecular Immunology, University Medical Center, Georg August University Göttingen, Göttingen, Germany.
⁴ Department of Internal Medicine III, University Hospital Regensburg, Regensburg, Germany.
⁵ Hematology and Medical Oncology, University Medical Center, Georg August University Göttingen, Göttingen, Germany.

^# Contributed equally.

Abstract

Introduction: Data on genomic susceptibility for adverse outcomes after hematopoietic stem cell transplantation (HSCT) for recipients are scarce.

Methods: We performed a genome wide association study (GWAS) to identify genes associated with survival/mortality, relapse, and severe graft-versus-host disease (sGvHD), fitting proportional hazard and subdistributional models to data of n=1,392 recipients of European ancestry from three centres.

Results: The single nucleotide polymorphism (SNP) rs17154454, intronic to the neuronal growth guidant semaphorin 3C gene (SEMA3C), was genome-wide significantly associated with event-free survival (p=7.0x10^-8) and sGvHD (p=7.5x10^-8). Further associations were detected for SNPs in the Paxillin gene (PXN) with death without prior relapse or sGvHD, as well as for SNPs of the Plasmacytoma Variant Translocation 1 gene (PVT1, a long non-coding RNA gene), the Melanocortin 5 Receptor (MC5R) gene and the WW Domain Containing Oxidoreductase gene (WWOX), all associated with the occurrence of sGvHD. Functional considerations support the observed associations.

Discussion: Thus, new genes were identified, potentially influencing the outcome of HSCT.

Keywords: GWAS; GvHD; HSCT; competing risks; survival.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Genome-Wide Association Study
Genomics
Graft vs Host Disease* / genetics
Hematopoietic Stem Cell Transplantation* / adverse effects
Humans
Recurrence

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. RD, HB and DK were supported by the Deutsche Forschungsgemeinschaft (GRK 1034). RD, AD and EH were supported by the European Commission Grant FP7-PEOPLE-2012-ITN-315963 (CELLEUROPE). RD, HB, AD, EH, RC and DW were supported by the European Cooperation in Science & Technology under the COST Action CA17138 (Integrated European Network on Chronic Graft Versus Host Disease: EUROGRAFT). RC was supported by the Newcastle Hospitals Charity (BH191620). We acknowledge support by the Open Access Publication Funds of the Göttingen University (manuscript number: 1280876).