From GWAS to function: lessons from blood cells

Abstract

Haematopoiesis, or the process of formation of mature blood cells from committed progenitors, represents an accessible and well‐studied paradigm of cell differentiation and lineage specification. Genetic association studies provide a powerful approach to discover new genes, biological pathways and mechanisms underlying haematopoietic development. Here, we highlight recent findings of genomewide association studies ( GWAS ) linking 145 genomic loci to traits affecting the formation of red and white cells and platelets in European and other ancestries. We present strategies to address the main challenges in GWAS discoveries, particularly to find functional and regulatory effects of genetic variants, and to identify genes through which these genetic variants affect haematological phenotypes. We argue that studies of haematological trait variation provide an ideal paradigm for understanding the function of GWAS ‐associated variants owing to the accessible nature of cells, simple cellular phenotype and focused efforts to characterize the genetic and epigenetic factors influencing the regulatory landscape in highly pure mature cell populations.