Genome-wide Trans-ethnic Meta-analysis Identifies Seven Genetic Loci Influencing Erythrocyte Traits and a Role for RBPMS in Erythropoiesis

Am J Hum Genet. 2017 Jan 5;100(1):51-63. doi: 10.1016/j.ajhg.2016.11.016. Epub 2016 Dec 22.

Abstract

Genome-wide association studies (GWASs) have identified loci for erythrocyte traits in primarily European ancestry populations. We conducted GWAS meta-analyses of six erythrocyte traits in 71,638 individuals from European, East Asian, and African ancestries using a Bayesian approach to account for heterogeneity in allelic effects and variation in the structure of linkage disequilibrium between ethnicities. We identified seven loci for erythrocyte traits including a locus (RBPMS/GTF2E2) associated with mean corpuscular hemoglobin and mean corpuscular volume. Statistical fine-mapping at this locus pointed to RBPMS at this locus and excluded nearby GTF2E2. Using zebrafish morpholino to evaluate loss of function, we observed a strong in vivo erythropoietic effect for RBPMS but not for GTF2E2, supporting the statistical fine-mapping at this locus and demonstrating that RBPMS is a regulator of erythropoiesis. Our findings show the utility of trans-ethnic GWASs for discovery and characterization of genetic loci influencing hematologic traits.

Publication types

  • Meta-Analysis

MeSH terms

  • Africa / ethnology
  • Alleles
  • Animals
  • Bayes Theorem
  • Continental Population Groups / genetics*
  • Erythrocytes / metabolism*
  • Erythropoiesis / genetics*
  • Ethnic Groups / genetics
  • Europe / ethnology
  • Far East / ethnology
  • Female
  • Genome-Wide Association Study
  • Humans
  • Linkage Disequilibrium
  • Male
  • RNA-Binding Proteins / genetics*
  • Zebrafish / genetics

Substances

  • RBPMS protein, human
  • RNA-Binding Proteins