PUBLICATION

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

Authors
van Rooij, F.J., 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., Ganesh, S.K.
ID
ZDB-PUB-161227-7
Date
2017
Source
American journal of human genetics   100(1): 51-63 (Journal)
Registered Authors
Ginsburg, David, Zhou, Yi, Zon, Leonard I.
Keywords
none
MeSH Terms
  • Asia, Eastern/ethnology
  • Male
  • Erythrocytes/metabolism*
  • Linkage Disequilibrium
  • Europe/ethnology
  • Africa/ethnology
  • Erythropoiesis/genetics*
  • Humans
  • Alleles
  • RNA-Binding Proteins/genetics*
  • Female
  • Racial Groups/genetics*
  • Bayes Theorem
  • Ethnicity/genetics
  • Zebrafish/genetics
  • Genome-Wide Association Study
  • Animals
(all 17)
PubMed
28017375 Full text @ Am. J. Hum. Genet.
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.
Genes / Markers
Figures
No images available
Show all Figures
Expression
Phenotype
Fish Conditions Stage Phenotype Figure
WT + MO1-rbpmsstandard conditions14-19 somites
WT + MO1-rbpmsstandard conditionsLong-pec
WT + MO1-rbpmsstandard conditionsLong-pec
1 - 3 of 3
Show
Mutations / Transgenics
No data available
Human Disease / Model
No data available
Sequence Targeting Reagents
Target Reagent Reagent Type
gtf2e2MO1-gtf2e2MRPHLNO
rbpmsMO1-rbpmsMRPHLNO
rbpms2aMO2-rbpms2aMRPHLNO
rbpms2bMO2-rbpms2bMRPHLNO
1 - 4 of 4
Show
Fish
Fish
WT
WT + MO1-gtf2e2
WT + MO1-rbpms
WT + MO2-rbpms2a
WT + MO2-rbpms2b
1 - 5 of 5
Show
Antibodies
Orthology
Engineered Foreign Genes
No data available
Mapping
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Citation
van Rooij, F.J., 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., Ganesh, S.K. (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):51-63.