Seventy-five genetic loci influencing the human red blood cell.

TitleSeventy-five genetic loci influencing the human red blood cell.
Publication TypeJournal Article
Year of Publication2012
Authorsvan der Harst P, Zhang W, Mateo Leach I, Rendon A, Verweij N, Sehmi J, Paul DS, Elling U, Allayee H, Li X et al.
Date Published2012 Dec 20
KeywordsAnimals, Cell Cycle, Cytokines, Drosophila melanogaster, Erythrocytes, Female, Gene Expression Regulation, Genetic Loci, Genome-Wide Association Study, Hematopoiesis, Hemoglobins, Humans, Male, Mice, Organ Specificity, Phenotype, Polymorphism, Single Nucleotide, RNA Interference, Signal Transduction

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.

Alternate JournalNature
PubMed ID23222517