Cardiac Allograft Injury In Patients Of African Ancestry: Trends Of Donor-Derived Cell-Free Dna Based On Genetic Ancestry

Purpose Higher rates of acute rejection in African American transplant recipients are reported across multiple organ types. Mechanisms underlying poorer outcomes vs. other races are poorly defined. Because race is a social construct, most studies use self-identified race to categorize patients. Reports of genetic unique to individuals of African ancestry (AA) led us to hypothesize that ancestry markers might enhance the precision of race categorization in studies of transplant injury and rejection. Methods Using the Genomic Research for Transplantation (GRAfT) cohort, we performed whole-genome genotyping assay and measured the donor-derived cell-free DNA (dd-cfDNA), a biomarker of graft injury. We genotyped 171 heart recipients and estimated the genetic ancestry proportions by GRAF-pop software referencing 1000Genome data. Applying the filters for African genetic ancestry proportion (AGAP), patients were categorized as AA if AGAP was \u003e 85%, and not of AA if AGAP 15%. Serial post-transplant plasma samples were analyzed for dd-cfDNA by Illumina HiSeq3500. We consolidated the highest dd-cfDNA level along the time series to represent each individual; data are presented as median + the standard error. To assess potential relationship between AGAP and dd-cfDNA, we selected patients at two extremes: 31 AAs (\u003e85% AGAP) and 97 non-AAs ( Results Among the 171 recipients, 69 self-reported as AAs (40%), while the AGAP reported 72 AAs (42 %). The consistence between self-reported and AGAP was 97.7% (167/171). AAs at the estimated extremes ( \u003e 85% AGAP) had significantly higher dd-cfDNA level than non-AAs ( 15% AGAP): 3.64 + 0.73 vs. 1.79 + 0.41, p=0.03). Self-reported race showed a non-significant trend towards higher dd-cfDNA levels in AAs compared to non-AAs: 2.91 + 0.48 vs. 1.79 + 0.40, p=0.074). Conclusion This study documents a high consistence between self-reported race and genetic ancestry markers. It also confirms our prior reports of increased graft injury reflected as higher levels of dd-cfDNA in AAs at the extremes of genetic ancestry proportion. Supporting our hypothesis, ancestry markers might augment self-reported race data, warranting further studies on the interaction genetic heterogeneity with social determinants of health.