A recipient variant correlated with DPB1 expression is associated with the risks of GVHD and relapse after unrelated HCT.
Larger cohorts would be needed to detect other genotypic associations with acute GVHD, chronic GVHD, and relapse after allogeneic HCT.
Previous studies have identified more than 200 genetic variants associated with acute or chronic graft-versus-host disease (GVHD) or recurrent malignancy after allogeneic hematopoietic cell transplantation (HCT). We tested these candidate donor and recipient variants in a cohort of 4270 HCT recipients of European ancestry and in sub-cohorts of 1827 sibling and 1447 unrelated recipients who had 10/10 HLA-A, B, C, DRB1, DQB1-matched donors. We also carried out a genome-wide association study (GWAS) for these same outcomes. The discovery and replication analysis of candidate variants identified a group of closely linked recipient HLA-DPB1 single-nucleotide polymorphisms (SNPs) associated with an increased risk of acute GVHD and a corresponding decreased risk of recurrent malignancy after unrelated HCT. These results reflect correlation with the level of HLA-DPB1 expression previously shown to affect the risks of acute GVHD and relapse in unrelated recipients. Our GWAS identified an association of chronic GVHD with a locus of X-linked recipient intron variants in NHS, a gene that regulates actin remodeling and cell morphology. Evaluation of this association in a second replication cohort did not confirm the original replication results, and we did not reach any definitive conclusion regarding the validity of this discovery. The cohort used for our study is larger than those used in most previous HCT studies but is smaller than those typically used for other genotype-phenotype association studies. Genomic and disease data from our study are available for further analysis in combination with data from other cohorts.