Genome-wide Trans-ethnic Meta-analysis Identifies Seven Genetic Loci Influencing Erythrocyte Traits and a Role for  RBPMS  in Erythropoiesis
Creators: name: Launer, Lenore J.
name: Zhou, Yi
name: Ridker, Paul M.
name: Fornage, Myriam
name: Jee, Sun Ha
name: Snively, Beverly M.
name: Morris, Andrew P.
name: Kamatani, Naoyuki
name: Gudnason, Vilmundur
name: Felix, Janine F.
name: Dehghan, Abbas
name: Chen, Yuan-Tsong
name: Trompouki, Eirini
name: Schmidt, Reinhold
name: Mueller, Christian
name: Becker, Diane M.
name: Ginsburg, David
name: Hayes, James
name: O'Donnell, Christopher J.
name: Rotter, Jerome I.
name: Desch, Karl C.
name: Zeller, Tanja
name: Okada, Yukinori
name: Coresh, Josef
name: Ford, Ian
name: Chu, Audrey Y.
name: Kooperberg, Charles
name: Levy, Daniel
name: Kubo, Michiaki
name: Chang, Li-Ching
name: Li, Jin
name: Lange, Leslie
name: Chen, Zhao
name: Becker, Lewis C.
name: Hu, Bella
name: Lambert, Amy J.
name: Mook-Kanamori, Dennis O.
name: Tang, Hua
name: Eiriksdottir, Gudny
name: Jukema, J. Wouter
name: Ferrucci, Luigi
name: Chasman, Daniel I.
name: Schmidt, Helena
name: Takahashi, Atsushi
name: Keating, Brendan
name: Stott, David J.
name: Yang, Qiong
name: Guralnik, Jack M.
name: Trompet, Stella
name: Cupples, L. Adrienne
name: Schick, Ursula M.
name: van Duijn, Cornelia M.
name: Brody, Jennifer A.
name: van Rooij, Frank J.A.
name: Psaty, Bruce M.
name: Abraham, Brian J.
name: Longo, Dan L.
name: Ghanbari, Mohsen
name: Saba, Yasaman
name: Slagboom, P. Eline
name: Uitterlinden, André G.
name: Harris, Tamara B.
name: Franco, Oscar H.
name: Keller, Margaux F.
name: Li-Gao, Ruifang
name: Tanaka, Toshiko
name: Reiner, Alexander P.
name: Kamatani, Yoichiro
name: Chen, Chien-Hsiun
name: Floyd, James S.
name: Hofman, Albert
name: Klein, Robert J.
name: Evans, Michelle K.
name: Tsai, Fuu-Jen
name: Matsuda, Koichi
name: Wilson, James G.
name: Yang, Min-Lee
name: Peters, Luanne L.
name: Li, Jun Z.
name: Wu, Jer-Yuarn
name: Nalls, Michael A.
name: Patel, Kushang V.
name: Zon, Leonard I.
name: Yanek, Lisa R.
name: Choudhuri, Avik
name: Ganesh, Santhi K.
name: Wild, Philipp S.
name: Fox, Caroline S.
name: Smith, Albert V.
name: Zonderman, Alan B.
name: Qayyum, Rehan
name: Chen, Ming-Huei
name: Grossmann, Vera
name: Johnson, Andrew D.
name: Ozel, Ayse B.
name: Boerwinkle, Eric
name: Yang, Song
name: Hofer, Edith
name: Yang, Jaden
name: Rice, Kenneth M.
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2017

description: Accession Numbers Summary data have been deposited in the database of Genotypes and Phenotypes (dbGaP) under CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology) Consortium Summary Results from Genomic Studies. The dbGaP study accession number is phs000930. Supplemental Data Supplemental data include Supplemental Acknowledgments, individual study methods and cohort descriptions, pleiotropy analysis, 10 tables, and a figure with 123 panels. Supplemental Data Document S1. Supplemental Acknowledgments, Individual Study Methods and Cohort Descriptions, Pleiotropy Analysis, and Figure S1 Download Data S1. Tables S1–S10 Download Document S2. Article plus Supplemental Data Download Web Resources Center for Genome Dynamics, http://cgd.jax.org dbGaP, http://www.ncbi.nlm.nih.gov/gap Matrix Spectral Decomposition, http://neurogenetics.qimrberghofer.edu.au/matSpD/ METASOFT 3.0c, http://www.buhmhan.com/software MGI Genes and Markers Query, http://www.informatics.jax.org/marker R/qtl v1.07-12, http://www.rqtl.org 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.