GVHD development in HSCT. (A) GVHD is an alloimmune response that develops after allogeneic transplantation, in which donor T cells recognize the host-derived alloantigens presented on their targets. In HLA-matched transplantation, these minor H antigens are typically defined by the host SNPs or by other polymorphisms that are not shared with the donor. GVHD development is also affected by other genetic and environmental factors. (B) The number of allele mismatches is defined as the number of alleles (0, 1, or 2) that are not shared by the donor. (C) Schematic diagram of the study design. For each SNP showing >5% of minor allele frequency in the donor cohort, association was tested between the presence/absence of grade II-IV aGVHD or grade III-IV aGVHD and the number of allele mismatches for each donor-recipient pair using log-rank and/or log-rank trend tests (GWAS), with corrections for multiple testing. GWAS was performed including the entire cohort, or to identify minor H antigen–related loci confined to those subsets sharing 1 of the 14 HLA alleles observed in >20% of the current transplant cohort. CTL, cytotoxic T lymphocyte; GWAS, genome-wide association study; JMDP, Japan Marrow Donor Program; mRNA, messenger RNA; TCR, T-cell receptor.