Array Genotyping of Transfusion Relevant Blood Cell Antigens in 6946 Ancestrally Diverse Subjects Open Access

• Array genotyping enables extensive blood cell antigen typing with >99.9% reproducibility across international laboratories.

• Accurate antigen genotyping by array in diverse populations provides an opportunity to reduce alloimmunization by extended matching.

Blood transfusions save millions of lives worldwide each year, yet formation of antibodies against non-self antigens remains a significant problem, particularly in frequently transfused patients. We designed and tested the Universal Blood Donor Typing (UBDT_PC1) array for automated high-throughput simultaneous typing of human erythroid, platelet, leukocyte, and neutrophil antigens (HEA, HPA, HLA, and HNA, respectively) to support selection of blood products matched beyond ABO/Rh. Typing samples from 6946 donors of European, African, Admixed American, South Asian, and East Asian ancestry at two different laboratories showed a genotype reproducibility of ≥99% for 17 244 variants, translating to 99.98%, 99.90%, and 99.93% concordance across 338 372 HEA, 53 270 HPA, and 107 094 HLA genotypes, respectively. Compared to previous clinical typing data, concordance was 99.9% and 99.6% for 245 874 HEA and 3726 HPA comparisons, respectively. HLA types were 99.1% concordant with clinical typing across 8130 comparisons, with imputation accuracy higher in Europeans versus non-Europeans. Seven variant RHD alleles, a GYPB deletion underlying the U− phenotype, and 14 high-frequency antigen negative types were also detected. Beyond blood typing, hereditary hemochromatosis-associated HFE variants were identified in 276 donors. We found that the UBDT_PC1 array can reliably type a wide range of blood cell antigens across diverse ancestries. Reproducibility and accuracy were retained when transfusion-relevant targets from the UBDT_PC1 array were incorporated into the UKBB_v2.2 genome-wide typing array. The results represent the potential for significant advancement towards improved patient care by reducing harm in transfused patients through extended matching.