Genome-wide Trans-ethnic Meta-analysis Identifies Seven Genetic Loci Influencing Erythrocyte Traits and a Role for RBPMS in Erythropoiesis.
Am J Hum Genet
; 100(1): 51-63, 2017 Jan 05.
Article
en En
| MEDLINE
| ID: mdl-28017375
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.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Proteínas de Unión al ARN
/
Grupos Raciales
/
Eritrocitos
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Eritropoyesis
Tipo de estudio:
Prognostic_studies
/
Systematic_reviews
Límite:
Animals
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Female
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Humans
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Male
País/Región como asunto:
Africa
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Asia
/
Europa
Idioma:
En
Revista:
Am J Hum Genet
Año:
2017
Tipo del documento:
Article
País de afiliación:
Países Bajos