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

Romina Petersen; John J. Lambourne; Biola M. Javierre; Luigi Grassi; Roman Kreuzhuber; Dace Ruklisa; Isabel M. Rosa; Ana R. Tomé; Heather Elding; Johanna P. van Geffen; Tao Jiang; Samantha Farrow; Jonathan Cairns; Abeer M. Al-Subaie; Sofie Ashford; Antony Attwood; Joana Batista; Heleen Bouman; Frances Burden; Fizzah A. Choudry; Laura Clarke; Paul Flicek; Stephen F. Garner; Matthias Haimel; Carly Kempster; Vasileios Ladopoulos; An-Sofie Lenaerts; Paulina M. Materek; Harriet McKinney; Stuart Meacham; Daniel Mead; Magdolna Nagy; Christopher J. Penkett; Augusto Rendon; Denis Seyres; Benjamin Sun; Salih Tuna; Marie-Elise van der Weide; Steven W. Wingett; Joost H. Martens; Oliver Stegle; Sylvia Richardson; Ludovic Vallier; David J. Roberts; Kathleen Freson; Lorenz Wernisch; Hendrik G. Stunnenberg; John Danesh; Peter Fraser; Nicole Soranzo; Adam S. Butterworth; Johan W. Heemskerk; Ernest Turro; Mikhail Spivakov; Willem H. Ouwehand; William J. Astle; Kate Downes; Myrto Kostadima; Mattia Frontini

doi:10.1038/ncomms16058

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

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

Romina Petersen, John J. Lambourne, Biola M. Javierre, Luigi Grassi, Roman Kreuzhuber, Dace Ruklisa, Isabel M. Rosa, Ana R. Tomé, Heather Elding, Johanna P. van Geffen, …

Nature communications, Vol.8(1), pp.1-12

13/07/2017

DOI: https://doi.org/10.1038/ncomms16058

PMCID: PMC5511350

PMID: 28703137

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. Numerous genetic variants, including those located in the non-coding regions of the genome, are known to be associated with blood cells traits. Here, Frontini and colleagues investigate their potential regulatory functions using epigenomic data and promoter long-range interactions.

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Title: Platelet function is modified by common sequence variation in megakaryocyte super enhancers
Creators - without role: Romina Petersen - National Health Service
John J. Lambourne - National Health Service
Biola M. Javierre - Babraham Institute
Luigi Grassi - University of Cambridge
Roman Kreuzhuber - European Bioinformatics Institute
Dace Ruklisa - MRC Biostatistics Unit
Isabel M. Rosa - National Health Service
Ana R. Tomé - National Health Service
Heather Elding - Wellcome Sanger Institute
Johanna P. van Geffen - Maastricht University
Tao Jiang - British Heart Foundation
Samantha Farrow - National Health Service
Jonathan Cairns - Babraham Institute
Abeer M. Al-Subaie - Imam Abdulrahman Bin Faisal University
Sofie Ashford - University of Cambridge
Antony Attwood - University of Cambridge
Joana Batista - National Health Service
Heleen Bouman - Wellcome Sanger Institute
Frances Burden - National Health Service
Fizzah A. Choudry - National Health Service
Laura Clarke - European Bioinformatics Institute
Paul Flicek - European Bioinformatics Institute
Stephen F. Garner - National Health Service
Matthias Haimel - University of Cambridge
Carly Kempster - National Health Service
Vasileios Ladopoulos - University of Cambridge
An-Sofie Lenaerts - Wellcome/MRC Cambridge Stem Cell Institute
Paulina M. Materek - Wellcome/MRC Cambridge Stem Cell Institute
Harriet McKinney - National Health Service
Stuart Meacham - University of Cambridge
Daniel Mead - Wellcome Sanger Institute
Magdolna Nagy - Maastricht University
Christopher J. Penkett - University of Cambridge
Augusto Rendon - National Health Service
Denis Seyres - University of Cambridge
Benjamin Sun - British Heart Foundation
Salih Tuna - University of Cambridge
Marie-Elise van der Weide - National Health Service
Steven W. Wingett - Babraham Institute
Joost H. Martens - Radboud University Nijmegen
Oliver Stegle - European Bioinformatics Institute
Sylvia Richardson - MRC Biostatistics Unit
Ludovic Vallier - Wellcome/MRC Cambridge Stem Cell Institute
David J. Roberts - University of Oxford
Kathleen Freson - KU Leuven
Lorenz Wernisch - MRC Biostatistics Unit
Hendrik G. Stunnenberg - Radboud University Nijmegen
John Danesh - Addenbrooke's Hospital
Peter Fraser - Florida State University
Nicole Soranzo - Wellcome Sanger Institute
Adam S. Butterworth - Addenbrooke's Hospital
Johan W. Heemskerk - Maastricht University
Ernest Turro - MRC Biostatistics Unit
Mikhail Spivakov - Babraham Institute
Willem H. Ouwehand - Addenbrooke's Hospital
William J. Astle - MRC Biostatistics Unit
Kate Downes - National Health Service
Myrto Kostadima - European Bioinformatics Institute
Mattia Frontini - National Health Service
Publication Details: Nature communications, Vol.8(1), pp.1-12
Publisher: Nature Publishing Group
Identifiers: 9914718608331
Academic Unit: Imam Abdulrahman Bin Faisal University
Language: English
Resource Type: Journal article