The Polygenic and Monogenic Basis of Blood Traits and Diseases

Dragana Vuckovic, Yoav Ben-Shlomo, Vijay G Sankaran*, Nicole Soranzo*

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

276 Citations (Scopus)
124 Downloads (Pure)


Blood cells play essential roles in human health, underpinning physiological processes such as immunity, oxygen transport, and clotting, which when perturbed cause a significant global health burden. Here we integrate data from UK Biobank and a large-scale international collaborative effort, including data for 563,085 European ancestry participants, and discover 5,106 new genetic variants independently associated with 29 blood cell phenotypes covering a range of variation impacting hematopoiesis. We holistically characterize the genetic architecture of hematopoiesis, assess the relevance of the omnigenic model to blood cell phenotypes, delineate relevant hematopoietic cell states influenced by regulatory genetic variants and gene networks, identify novel splice-altering variants mediating the associations, and assess the polygenic prediction potential for blood traits and clinical disorders at the interface of complex and Mendelian genetics. These results show the power of large-scale blood cell trait GWAS to interrogate clinically meaningful variants across a wide allelic spectrum of human variation.
Original languageEnglish
Pages (from-to)1214-1231 E11
Number of pages30
Issue number5
Early online date3 Sept 2020
Publication statusE-pub ahead of print - 3 Sept 2020


  • blood
  • genetics
  • hematopoiesis
  • rare diseases
  • polygenic risk
  • fine-mapping
  • splicing
  • UK Biobank
  • omnigenic
  • chromatin


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