Repository logo
 

Platelet function is modified by common sequence variation in megakaryocyte super enhancers

Published version
Peer-reviewed

Type

Article

Change log

Authors

Petersen, R 
Lambourne, JJ 
Javierre, BM 
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

Volume Title

8

Publisher

Springer Nature
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 (G0800270/1)
European Commission (279233)