Massively Parallel Reporter Assay of Rare non-coding variants with high impact in blood traits
Understanding the functional consequences of genetic variants associated with human traits and diseases —particularly those in non-coding regions—remains a significant challenge. Here we use analyses based on natural genetic variation and genetic engineering approaches to dissect the function of  94 non-coding variants associated with  haematological traits. We describe 22 genetic variants with impact on haematological variation through gene expression. Further,  through in-depth functional analysis, we illustrate how a rare, non-coding variant near the CUX1 transcription factor impacts on megakaryopoiesis through modulation of the CUX1 transcriptional cascade. With this work we advance the understanding of  the translational value of association studies  for variants implicated in blood and immunity.