The heritability of metabolite concentrations in stored human red blood cells


  • This publication was supported by the National Center for Advancing Translational Sciences, through Grant 2UL1TR000442, and National Institutes of Health Grants R01 GM073929, R01 CA169046, P42 ES013661, and P30 ES05605. Core facilities were supported in part by the Holden Comprehensive Cancer Center, P30 CA086862.



The degeneration of red blood cells (RBCs) during storage is a major issue in transfusion medicine. Family studies in the 1960s established the heritability of the RBC storage lesion based on poststorage adenosine triphosphate (ATP) concentrations. However, this critical discovery has not been further explored. In a classic twin study we confirmed the heritability of poststorage ATP concentrations and established the heritability of many other RBC metabolites.

Study Design and Methods

ATP concentrations and metabolomic profiles were analyzed in RBC samples from 18 twin pairs. On samples stored for 28 days, the heritability of poststorage ATP concentrations were 64 and 53% in CP2D- and AS-3–stored RBCs, respectively.


Metabolomic analyses identified 87 metabolites with an estimated heritability of 20% or greater. Thirty-six metabolites were significantly correlated with ATP concentrations (p ≤ 0.05) and 16 correlated with borderline significance (0.05 ≤ p ≤ 0.10). Of the 52 metabolites that correlated significantly with ATP, 24 demonstrated 20% or more heritability. Pathways represented by heritable metabolites included glycolysis, membrane remodeling, redox homeostasis, and synthetic and degradation pathways.


We conclude that many RBC metabolite concentrations are genetically influenced during storage. Future studies of key metabolic pathways and genetic modifiers of RBC storage could lead to major advances in RBC storage and transfusion therapy.