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Genome-Wide Association Study and Predictors of Neonatal Blood Cell Traits in Hispanic Newborns

This study leverages cord blood samples from the NHLBI's Umbilical Cord Blood Unit Collection to conduct genome-wide association studies (GWAS) of neonatal blood cell traits in newborns of Hispanic ethnicity. Cord blood (CB) aliquots from 382 de-identified newborns of Hispanic ethnicity were obtained from the NHLBI Biologic Specimen and Data Repository Information Coordinating Center (BioLINCC) through Project Request #11595. The CB samples were originally collected between 1998-2001 as part of the COBLT (Cord Blood Transplantation) study. Briefly, the COBLT study primarily aimed to (i) build ethnically diverse public cord blood banks with standardized collection/processing protocols and (ii) to conduct a prospective phase II trial of unrelated cord-blood transplantation in pediatric and adult candidates for allogeneic hematopoietic stem cell transplantation. The collected CB units and aliquots are currently maintained by BioLINCC, with samples available from donors with diverse racial/ethnic background.

All COBLT CB samples were red cell depleted, volume reduced and cryopreserved with DMSO/Dextran in 25 ml bags. Test aliquots were used by COBLT for flow cytometry to characterize predictors of time to engraftment for CB samples. Cell surface markers assessed included CD34, CD45, CD3, CD8, CD4, CD19, CD16, and CD56. CB aliquots were requested from subjects reported as Hispanic in the NHLBI Umbilical Cord Blood Unit Collection. Epidemiological data and cell-related indices were obtained from the Umbilical Cord Blood Unit Collection repository.

To investigate genetic variation associated with blood cell traits measured in the Hispanic newborn samples, we isolated DNA from CB and conducted genome-wide SNP genotyping using the Axiom PangenomiX array (Thermo Fisher). Whole-genome imputation was performed using the TOPMed Imputation Server, and GWAS of 24 blood and immune cell traits were conducted in up to 382 Hispanic newborns for each trait.