Genome-wide Trans-ethnic Meta-analysis Identifies Seven Genetic Loci Influencing Erythrocyte Traits and a Role for RBPMS in Erythropoiesis.
Document Type
Article
Publication Date
1-5-2017
JAX Source
Am J Hum Genet 2017 Jan 5; 100(1):51-63
Volume
100
Issue
1
First Page
51
Last Page
63
ISSN
1537-6605
PMID
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. Am J Hum Genet 2017 Jan 5; 100(1):51-63.
Recommended Citation
van Rooij F,
Qayyum R,
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Zhou Y,
Trompet S,
Tanaka T,
Keller M,
Chang L,
Schmidt H,
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O'Donnell C,
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Cupples L,
Nalls M,
Morris A,
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Zon L,
Ganesh S.
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