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

Petersen R; Lambourne JJ; Javierre BM; Grassi L; Kreuzhuber R; Ruklisa D; Rosa IM; Tomé AR; Elding H; van Geffen JP; Jiang T; Farrow S; Cairns J; Al-Subaie AM; Ashford S; Attwood A; Batista J; Bouman H; Burden F; Choudry FA; Clarke L; Flicek P; Garner SF; Haimel M; Kempster C; Ladopoulos V; Lenaerts AS; Materek PM; McKinney H; Meacham S; Mead D; Nagy M; Penkett CJ; Rendon A; Seyres D; Sun B; Tuna S; van der Weide ME; Wingett SW; Martens JH; Stegle O; Richardson S; Vallier L; Roberts DJ; Freson K; Wernisch L; Stunnenberg HG; Danesh J; Fraser P; Soranzo N; Butterworth AS; Heemskerk JW; Turro E; Spivakov M; Ouwehand WH; Astle WJ; Downes K; Kostadima M; Frontini M.


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.

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