Anaemia is a chief determinant of global ill health, contributing to cognitive impairment, growth retardation and impaired physical capacity. To understand further the genetic factors influencing red blood cells, we carried out a genome-wide association study of haemoglobin concentration and related parameters in up to 135,367 individuals. Here we identify 75 independent genetic loci associated with one or more red blood cell phenotypes at P < 10−8, which together explain 4–9% of the phenotypic variance per trait. Using expression quantitative trait loci and bioinformatic strategies, we identify 121 candidate genes enriched in functions relevant to red blood cell biology. The candidate genes are expressed preferentially in red blood cell precursors, and 43 have haematopoietic phenotypes in Mus musculus or Drosophila melanogaster. Through open-chromatin and coding-variant analyses we identify potential causal genetic variants at 41 loci. Our findings provide extensive new insights into genetic mechanisms and biological pathways controlling red blood cell formation and function. A series of genetic studies have led to the discovery of novel independent loci and candidate genes associated with red blood cell phenotype; for a proportion of these genes potential single-nucleotide genetic variants are also identified, providing new insights into genetic pathways controlling red blood cell formation, function and pathology. This genome-wide association study of more than 135,000 individuals identifies 75 independent genetic loci influencing red blood cell phenotypes, enriched for genes involved in cell cycle control, transcriptional regulation, growth factor and cytokine signalling, haemoglobin synthesis, iron handling and cytoskeletal function, as well as a number of genes of uncertain or unknown function. Further analyses identified 121 candidate genes related to red blood cell biology, one-third of which have haematopoietic phenotypes in mouse and Drosophila.

Seventy-five genetic loci influencing the human red blood cell