Platelet function is modified by common sequence variation in megakaryocyte super enhancers.
Romina PetersenJohn J LambourneBiola M JavierreLuigi GrassiRoman KreuzhuberDace RuklisaIsabel M RosaAna R ToméHeather EldingJohanna P van GeffenTao JiangSamantha FarrowJonathan CairnsAbeer M Al-SubaieSofie AshfordAntony AttwoodJoana BatistaHeleen BoumanFrances BurdenFizzah A ChoudryLaura ClarkePaul FlicekStephen F GarnerMatthias HaimelCarly KempsterVasileios LadopoulosAn-Sofie LenaertsPaulina M MaterekHarriet McKinneyStuart MeachamDaniel MeadMagdolna NagyChristopher J PenkettAugusto RendonDenis SeyresBenjamin SunSalih TunaMarie-Elise van der WeideSteven W WingettJoost H MartensOliver StegleSylvia RichardsonLudovic VallierDavid J RobertsKathleen FresonLorenz WernischHendrik G StunnenbergJohn DaneshPeter FraserNicole SoranzoAdam S ButterworthJohan W HeemskerkErnest TurroMikhail SpivakovWillem H OuwehandWilliam J AstleKate DownesMyrto KostadimaMattia FrontiniPublished in: Nature communications (2017)
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.