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van Rooij, Frank J.A.; Qayyum, Rehan; Smith, Albert V.; Zhou, Yi; Trompet, Stella; Tanaka, Toshiko; Keller, Margaux F.; Chang, Li-Ching; Schmidt, Helena; Yang, Min-Lee; Chen, Ming-Huei; Hayes, James; Johnson, Andrew D.; Yanek, Lisa R.; Mueller, Christian; Lange, Leslie; Floyd, James S.; Ghanbari, Mohsen; Zonderman, Alan B.; Jukema, J. Wouter; Hofman, Albert; van Duijn, Cornelia M.; Desch, Karl C.; Saba, Yasaman; Ozel, Ayse B.; Snively, Beverly M.; Wu, Jer-Yuarn; Schmidt, Reinhold; Fornage, Myriam; Klein, Robert J. ... view all 100 authors View less authors (2016)
Publisher: Elsevier
Languages: English
Types: Article
Subjects: Article, R1
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.

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