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Abstract Neutrophils play fundamental roles in innate inflammatory response, shape adaptive immunity 1 , and have been identified as a potentially causal cell type underpinning genetic associations with immune system traits and diseases 2,3 The majority of these variants are non-coding and the underlying mechanisms are not fully understood. Here, we profiled the binding of one of the principal myeloid transcriptional regulators, PU.1, in primary neutrophils across nearly a hundred volunteers, and elucidate the coordinated genetic effects of PU.1 binding variation, local chromatin state, promoter-enhancer interactions and gene expression. We show that PU.1 binding and the associated chain of molecular changes underlie genetically-driven differences in cell count and autoimmune disease susceptibility. Our results advance interpretation for genetic loci associated with neutrophil biology and immune disease.

Original publication

DOI

10.1101/620260

Type

Journal article

Publication Date

29/04/2019