Variation in immune cellular homeostasis exists between individuals, is heritable and due to genes and environment. Environmental influences increase with age, masking genetic determinants and barring human adult studies from informing on the origin of baseline variability.To identify genetic factors affecting individuals' immune profile in early life we profiled the bone marrow of 55 genetically diverse Collaborative Cross mouse strains, using high resolution masscytometry. We identified 1,662 genes associated with 11 well defined cell subsets, 862 of which validated in an independent cohort. These genes were strongly enriched for basic housekeeping functions of proliferation and death, predicted cellular abundance and showed a higher mutation rate across multiple human cancers. Thus, akin to mRNA or protein species abundance, cellular variation is determined by genetic variants of production and turnover genes. Given these affect baseline homeostasis, reaching an at-risk immune state would differ for individuals, set by the genetic determinants we identified here.
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