Manuel Tardaguila, Dominique Von Schiller, Michela Colombo, Ilaria Gori, Eve L. Coomber et al.
Understanding the function of genetic variants associated with human traits and diseases remains a significant challenge. Here, we combined analyses based on natural genetic variation and genetic engineering to dissect the function of 94 non-coding variants associated with hematological traits. We describe 22 genetic variants impacting hematological variation through gene expression. Further, through in-depth functional analysis, we illustrate how a rare, non-coding variant near the CUX1 transcription factor impacts megakaryopoiesis through the modulation of the CUX1 transcriptional cascade. Collectively, our findings enhance the functional interpretation of genetic association studies and advance understanding of how non-coding variants contribute to blood and immune system variation.
Manuel Tardaguila, Dominique Von Schiller, Michela Colombo, Ilaria Gori, Eve L. Coomber, Thomas Vanderstichele, Paola Benaglio, Chiara Chiereghin, Sebastian Gerety, Dragana Vuckovic, Arianna Landini, Giuditta Clerici, Aurora Casiraghi, Patrick Albers, Helen Ray-Jones, Katie L. Burnham, Alex Tokolyi, Elodie Persyn, Mikhail Spivakov, Vijay G. Sankaran, Klaudia Walter, Kousik Kundu, Nicola Pirastu, Michael Inouye, Dirk S. Paul, Emma E. Davenport, Pelin Sahlén, Stephen Watt, Nicole Soranzo. Integrating natural and engineered genetic variations to decode regulatory influence on blood traits. 2026-02-03. https://doi.org/10.1016/j.celrep.2026.116937
The 19,050-oligonucleotide allele-specific barcoded library was nucleofected into human THP-1 acute monocytic leukemia cells in seven replicates. Table S4 provides 137 cross-tile meta-analysis rows for index-variant, control, and diplotype comparisons.
The 19,050-oligonucleotide allele-specific barcoded library was nucleofected into human K-562 chronic myeloid leukemia cells in seven replicates. Table S4 provides 137 cross-tile meta-analysis rows for index-variant, control, and diplotype comparisons.
The 19,050-oligonucleotide allele-specific barcoded library was nucleofected into human HL-60 acute myeloid leukemia cells in seven replicates. Table S4 provides 137 cross-tile meta-analysis rows for index-variant, control, and diplotype comparisons.
The 19,050-oligonucleotide allele-specific barcoded library was nucleofected into human CHRF-288-11 acute megakaryoblastic leukemia cells in seven replicates. Table S4 provides 137 cross-tile meta-analysis rows for index-variant, control, and diplotype comparisons.
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