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



van Rooij, Frank JA, Qayyum, Rehan, Smith, Albert V, Zhou, Yi, Trompet, Stella, Tanaka, Toshiko, Keller, Margaux F, Chang, Li-Ching, Schmidt, Helena, Yang, Min-Lee
et al (show 90 more authors) (2017) Genome-wide Trans-ethnic Meta-analysis Identifies Seven Genetic Loci Influencing Erythrocyte Traits and a Role for <i>RBPMS</i> in Erythropoiesis. AMERICAN JOURNAL OF HUMAN GENETICS, 100 (1). pp. 51-63.

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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.

Item Type: Article
Uncontrolled Keywords: BioBank Japan Project, Erythrocytes, Animals, Zebrafish, Humans, RNA-Binding Proteins, Bayes Theorem, Erythropoiesis, Linkage Disequilibrium, Alleles, Africa, Europe, Female, Male, Genome-Wide Association Study, Ethnicity, Racial Groups, Asia, Eastern
Depositing User: Symplectic Admin
Date Deposited: 20 Jan 2017 09:07
Last Modified: 12 Oct 2023 13:52
DOI: 10.1016/j.ajhg.2016.11.016
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3005279