AUTHOR=Rosenberger Albert , Crossland Rachel E. , Dressel Ralf , Kube Dieter , Wolff Daniel , Wulf Gerald , Bickeböller Heike , Dickinson Anne , Holler Ernst 

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

JOURNAL=Frontiers in Immunology

VOLUME=15

YEAR=2024

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1280876

DOI=10.3389/fimmu.2024.1280876

ISSN=1664-3224

ABSTRACT=<sec><title>Introduction</title><p>Data on genomic susceptibility for adverse outcomes after hematopoietic stem cell transplantation (HSCT) for recipients are scarce.</p></sec><sec><title>Methods</title><p>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.</p></sec><sec><title>Results</title><p>The single nucleotide polymorphism (SNP) rs17154454, intronic to the neuronal growth guidant semaphorin 3C gene (<italic>SEMA3C)</italic>, was genome-wide significantly associated with event-free survival (p=7.0x10<sup>-8</sup>) and sGvHD (p=7.5x10<sup>-8</sup>). Further associations were detected for SNPs in the Paxillin gene (<italic>PXN) with</italic> death without prior relapse or sGvHD, as well as for SNPs of the Plasmacytoma Variant Translocation 1 gene <italic>(PVT1</italic>, a long non-coding RNA gene<italic>)</italic>, the Melanocortin 5 Receptor <italic>(MC5R) gene</italic> and the WW Domain Containing Oxidoreductase gene (<italic>WWOX)</italic>, all associated with the occurrence of sGvHD. Functional considerations support the observed associations.</p></sec><sec><title>Discussion</title><p>Thus, new genes were identified, potentially influencing the outcome of HSCT.</p></sec>