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

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.