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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.

Original publication




Journal article



Publication Date





1415 - 1429.e19


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