Platelet function is modified by common sequence variation in megakaryocyte super enhancers
Published version
Peer-reviewed
Repository URI
Repository DOI
Change log
Authors
Petersen, R
Lambourne, JJ
Javierre, BM
Grassi, Luigi https://orcid.org/0000-0002-6308-7540
Kreuzhuber, R
Abstract
Linking non-coding genetic variants associated with the risk of diseases or disease-relevant traits to target genes is a crucial step to realize GWAS potential in the introduction of precision medicine. Here we set out to determine the mechanisms underpinning variant association with platelet quantitative traits using cell type-matched epigenomic data and promoter long-range interactions. We identify potential regulatory functions for 423 of 565 (75%) non-coding variants associated with platelet traits and we demonstrate, through ex vivo and proof of principle genome editing validation, that variants in super enhancers play an important role in controlling archetypical platelet functions.
Description
Keywords
Blood Platelets, Chromatin, Enhancer Elements, Genetic, Erythroblasts, Genetic Variation, Humans, Megakaryocytes, Promoter Regions, Genetic
Journal Title
Nature Communications
Conference Name
Journal ISSN
2041-1723
2041-1723
2041-1723
Volume Title
8
Publisher
Springer Nature
Publisher DOI
Sponsorship
Medical Research Council (G0800270)
Medical Research Council (MR/L003120/1)
Medical Research Council (MC_PC_12009)
MRC (unknown)
MRC (unknown)
European Commission (282510)
European Research Council (268834)
Medical Research Council (MR/K024043/1)
European Commission Horizon 2020 (H2020) Spreading Excellence and Widening Participation (692041)
British Heart Foundation (None)
British Heart Foundation (None)
Medical Research Council (MR/L003120/1)
Medical Research Council (MC_PC_12009)
MRC (unknown)
MRC (unknown)
European Commission (282510)
European Research Council (268834)
Medical Research Council (MR/K024043/1)
European Commission Horizon 2020 (H2020) Spreading Excellence and Widening Participation (692041)
British Heart Foundation (None)
British Heart Foundation (None)