Lessons and Implications from Genome-Wide Association Studies (GWAS) Findings of Blood Cell Phenotypes.
Genome-wide association studies (GWAS) have identified reproducible genetic associations with hundreds of human diseases and traits. The vast majority of these associated single nucleotide polymorphisms (SNPs) are non-coding, highlighting the challenge in moving from genetic findings to mechanistic and functional insights. Nevertheless, large-scale (epi)genomic studies and bioinformatic analyses strongly suggest that GWAS hits are not randomly distributed in the genome but rather pinpoint specific biological pathways important for disease development or phenotypic variation. In this review, we focus on GWAS discoveries for the three main blood cell types: red blood cells, white blood cells and platelets. We summarize the knowledge gained from GWAS of these phenotypes and discuss their possible clinical implications for common (e.g., anemia) and rare (e.g., myeloproliferative neoplasms) human blood-related diseases. Finally, we argue that blood phenotypes are ideal to study the genetics of complex human traits because they are fully amenable to experimental testing.
Montreal Heart Institute, Faculté de Médecine, Université de Montréal, 5000 Bélanger Street, Montréal, QC H1T 1C8, Canada. nathalie.chami@mhi-humangenetics.org.
Nathalie
N
Chami
Montreal Heart Institute, Faculté de Médecine, Université de Montréal, 5000 Bélanger Street, Montréal, QC H1T 1C8, Canada. guillaume.lettre@umontreal.ca.
Guillaume
G
Lettre