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

van Rooij, F. J.A. et al. (2017) Genome-wide trans-ethnic meta-analysis Identifies seven genetic loci influencing erythrocyte traits and a role for RBPMS in erythropoiesis. American Journal of Human Genetics, 100(1), pp. 51-63. (doi: 10.1016/j.ajhg.2016.11.016) (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.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Stott J, Professor David and Ford, Professor Ian
• Authors: van Rooij, F. J.A., Qayyum, R., Smith, A. V., Zhou, Y., Trompet, S., Tanaka, T., Keller, M. F., Chang, L.-C., Schmidt, H., Yang, M.-L., Chen, M.-H., Hayes, J., Johnson, A. D., Yanek, L. R., Mueller, C., Lange, L., Floyd, J. S., Ghanbari, M., Zonderman, A. B., Jukema, J. W., Hofman, A., van Duijn, C. M., Desch, K. C., Saba, Y., Ozel, A. B., Snively, B. M., Wu, J.-Y., Schmidt, R., Fornage, M., Klein, R. J., Fox, C. S., Matsuda, K., Kamatani, N., Wild, P. S., Stott, D. J., Ford, I., Slagboom, P. E., Yang, J., Chu, A. Y., Lambert, A. J., Uitterlinden, A. G., Franco, O. H., Hofer, E., Ginsburg, D., Hu, B., Keating, B., Schick, U. M., Brody, J. A., Li, J. Z., Chen, Z., Zeller, T., Guralnik, J. M., Chasman, D. I., Peters, L. L., Kubo, M., Becker, D. M., Li, J., Eiriksdottir, G., Rotter, J. I., Levy, D., Grossmann, V., Patel, K. V., Chen, C.-H., Ridker, P. M., Tang, H., Launer, L. J., Rice, K. M., Li-Gao, R., Ferrucci, L., Evans, M. K., Choudhuri, A., Trompouki, E., Abraham, B. J., Yang, S., Takahashi, A., Kamatani, Y., Kooperberg, C., Harris, T. B., Jee, S. H., Coresh, J., Tsai, F.-J., Longo, D. L., Chen, Y.-T., Felix, J. F., Yang, Q., Psaty, B. M., Boerwinkle, E., Becker, L. C., Mook-Kanamori, D. O., Wilson, J. G., Gudnason, V., O'Donnell, C. J., Dehghan, A., Cupples, L. A., Nalls, M. A., Morris, A. P., Okada, Y., Reiner, A. P., Zon, L. I., and Ganesh, S. K.
• Subjects: R Medicine > R Medicine (General)
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health; College of Medical Veterinary and Life Sciences > School of Health & Wellbeing > Robertson Centre
• Journal Name: American Journal of Human Genetics
• Publisher: Elsevier (Cell Press)
• ISSN: 0002-9297
• ISSN (Online): 1537-6605
• Published Online: 22 December 2016
• Copyright Holders: Copyright © 2017 American Society of Human Genetics
• First Published: First published in American Journal of Human Genetics 100(1): 51-63
• Publisher Policy: Reproduced in accordance with the publisher copyright policy