Genome-wide trans-ethnic meta-analysis Identifies seven genetic loci influencing erythrocyte traits and a role for RBPMS in erythropoiesis

Article, Other literature type English OPEN
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 (2017)

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.