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

Authors: 
van Rooij FJ, Qayyum R, Smith AV, Zhou Y, Trompet S, Tanaka T, Keller MF, Chang LC, Schmidt H, Yang ML, Chen MH, Hayes J, Johnson AD, Yanek LR, Mueller C, Lange L, Floyd JS, Ghanbari M, Zonderman AB, Jukema JW, Hofman A, van Duijn CM, Desch KC, Saba Y, Ozel AB, Snively BM, Wu JY, Schmidt R, Fornage M, Klein RJ, Fox CS, Matsuda K, Kamatani N, Wild PS, Stott DJ, Ford I, Slagboom PE, Yang J, Chu AY, Lambert AJ, Uitterlinden AG, Franco OH, Hofer E, Ginsburg D, Hu B, Keating B, Schick UM, Brody JA, Li JZ, Chen Z, Zeller T, <authors deleted - database limit> Yang Q, Psaty BM, Boerwinkle E, Becker LC, Mook-Kanamori DO, Wilson JG, Gudnason V, O'Donnell CJ, Dehghan A, Cupples LA, Nalls MA, Morris AP, Okada Y, Reiner AP, Zon LI, Ganesh SK
Citation: 
Am J Hum Genet. 2016 Dec 19. pii: S0002-9297(16)30520-1. doi: 10.1016/j.ajhg.2016.11.016. [Epub ahead of print]
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.
Epub: 
Yes
Link to Publication: 
http://www.cell.com/ajhg/abstract/S0002-9297(16)30520-1
Organism or Cell Type: 
zebrafish