Seventy-five genetic loci influencing the human red blood cell
Van Der Harst P., Zhang W., Mateo Leach I., Rendon A., Verweij N., Sehmi J., Paul DS., Elling U., Allayee H., Li X., Radhakrishnan A., Tan ST., Voss K., Weichenberger CX., Albers CA., Al-Hussani A., Asselbergs FW., Ciullo M., Danjou F., Dina C., Esko T., Evans DM., Franke L., Gögele M., Hartiala J., Hersch M., Holm H., Hottenga JJ., Kanoni S., Kleber ME., Lagou V., Langenberg C., Lopez LM., Lyytikäinen LP., Melander O., Murgia F., Nolte IM., O'Reilly PF., Padmanabhan S., Parsa A., Pirastu N., Porcu E., Portas L., Prokopenko I., Ried JS., Shin SY., Tang CS., Teumer A., Traglia M., Ulivi S., Westra HJ., Yang J., Hua Zhao J., Anni F., Abdellaoui A., Attwood A., Balkau B., Bandinelli S., Bastardot F., Benyamin B., Boehm BO., Cookson WO., Das D., De Bakker PIW., De Boer RA., De Geus EJC., De Moor MH., Dimitriou M., Domingues FS., Döring A., Engström G., Eyjolfsson GI., Ferrucci L., Fischer K., Galanello R., Garner SF., Genser B., Gibson QD., Girotto G., Gudbjartsson DF., Harris SE., Hartikainen AL., Hastie CE., Hedblad B., Illig T., Jolley J., Kähönen M., Kema IP., Kemp JP., Liang L., Lloyd-Jones H., Loos RJF., Meacham S., Medland SE., Meisinger C., Memari Y., Mihailov E., Miller K., Moffatt MF., Nauck M.
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. © 2012 Macmillan Publishers Limited. All rights reserved.