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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.

Original publication

DOI

10.1016/j.ajhg.2016.11.016

Type

Journal article

Journal

Am J Hum Genet

Publication Date

05/01/2017

Volume

100

Pages

51 - 63

Keywords

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