Integrating natural and engineered genetic variations to decode regulatory influence on blood traits

Cell Reports 2026 Open access

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Authors: Manuel Tardáguila, Dominique Von Schiller, M. Colombo, Ilaria Gori, Eve L. Coomber, Thomas Vanderstichele, Paola Benaglio, Chiara Chiereghin, Sebastian Gerety, Dragana Vuckovic, Arianna Landini, Giuditta Clerici
+17 more Aurora Casiraghi, Patrick Albers, Helen F. Ray-Jones, Katie L. Burnham, Alex Tokolyi, Elodie Persyn, Mikhail Spivakov, Vijay G. Sankaran, Klaudia Walter, Kousik Kundu, Nicola Pirastu, Michael Inouye, Paul Dirk, Emma E. Davenport, Pelin Sahlén, Stephen Watt, Nicole Soranzo
DOI: 10.1016/j.celrep.2026.116937
Cited by: 1
References: 78

Abstract

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.

Fields of Study & Subjects

Genetic Associations and Epidemiology Blood groups and transfusion Genomics and Rare Diseases

Publication details

Journal / source
Cell Reports
Publisher
Elsevier BV
Volume
45
Issue
2
Pages
116937–116937
Publication date
1 February 2026
Language
EN