In The Blood: Connecting Variant to Function In Human Hematopoiesis

Trends Genet. 2020 Aug;36(8):563-576. doi: 10.1016/j.tig.2020.05.006. Epub 2020 Jun 10.

Abstract

Genome-wide association studies (GWAS) have identified thousands of genetic variants associated with a range of human diseases and traits. However, understanding the mechanisms by which these genetic variants have an impact on associated diseases and traits, often referred to as the variant-to-function (V2F) problem, remains a significant hurdle. Solving the V2F challenge requires us to identify causative genetic variants, relevant cell types/states, target genes, and mechanisms by which variants can cause diseases or alter phenotypic traits. We discuss emerging functional approaches that are being applied to tackle the V2F problem for blood cell traits, illuminating how human genetic variation can impact on key mechanisms in hematopoiesis, as well as highlighting future prospects for this nascent field.

Keywords: GWAS; blood cell traits; hematopoiesis; variant to function.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Genetic Association Studies
  • Genetic Predisposition to Disease*
  • Genetic Variation*
  • Genome-Wide Association Study
  • Hematologic Diseases / blood
  • Hematologic Diseases / diagnosis
  • Hematologic Diseases / genetics*
  • Hematologic Diseases / therapy
  • Hematopoiesis*
  • Humans
  • Phenotype*
  • Quantitative Trait Loci*