Astle WJ Elding H Jiang T Allen D Ruklisa D Mann AL Mead D Bouman H Riveros-Mckay F Kostadima MA Lambourne JJ Sivapalaratnam S Downes K Kundu K Bomba L Berentsen K Bradley JR Daugherty LC Delaneau O Freson K Garner SF Grassi L Guerrero J Haimel M Janssen-Megens EM Kaan A Kamat M Kim B Mandoli A Marchini J Martens JHA Meacham S Megy K O'Connell J Petersen R Sharifi N Sheard SM Staley JR Tuna S van der Ent M Walter K Wang SY Wheeler E Wilder SP Iotchkova V Moore C Sambrook J Stunnenberg HG Di Angelantonio E Kaptoge S Kuijpers TW Carrillo-de-Santa-Pau E Juan D Rico D Valencia A Chen L Ge B Vasquez L Kwan T Garrido-Martín D Watt S Yang Y Guigo R Beck S Paul DS Pastinen T Bujold D Bourque G Frontini M Danesh J Roberts DJ Ouwehand WH Butterworth AS Soranzo N 2016 Many common variants have been associated with hematological traits, but identification of causal genes and pathways has proven challenging. We performed a genome-wide association analysis in the UK Biobank and INTERVAL studies, testing 29.5 million genetic variants for association with 36 red cell, white cell, and platelet properties in 173,480 European-ancestry participants. This effort yielded hundreds of low frequency (<5%) and rare (<1%) variants with a strong impact on blood cell phenotypes. Our data highlight general properties of the allelic architecture of complex traits, including the proportion of the heritable component of each blood trait explained by the polygenic signal across different genome regulatory domains. Finally, through Mendelian randomization, we provide evidence of shared genetic pathways linking blood cell indices with complex pathologies, including autoimmune diseases, schizophrenia, and coronary heart disease and evidence suggesting previously reported population associations between blood cell indices and cardiovascular disease may be non-causal. application/pdf https://sonar.ch/global/documents/232625 eng info:eu-repo/semantics/altIdentifier/doi/10.1016/j.cell.2016.10.042 info:eu-repo/semantics/altIdentifier/pmid/27863252 info:eu-repo/semantics/openAccess Cell. - 2016 Mendelian randomization autoimmune diseases blood cardiovascular diseases complex disease epigenetics genetics hematology hematopoiesis Alleles Cell Differentiation European Continental Ancestry Group Genetic Predisposition to Disease Genetic Variation Genome-Wide Association Study Hematopoietic Stem Cells Humans Immune System Diseases Polymorphism, Single Nucleotide Quantitative Trait Loci The Allelic Landscape of Human Blood Cell Trait Variation and Links to Common Complex Disease. http://purl.org/coar/resource_type/c_6501