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

Collapse authors list.
van Rooij, Frank JA, Qayyum, Rehan, Smith, Albert V, Zhou, Yi, Trompet, Stella, Tanaka, Toshiko, Keller, Margaux F, Chang, Li-Ching, Schmidt, Helena, Yang, Min-Lee et al (show 90 more authors) , 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, Fox, Caroline S, Matsuda, Koichi, Kamatani, Naoyuki, Wild, Philipp S, Stott, David J, Ford, Ian, Slagboom, P Eline, Yang, Jaden, Chu, Audrey Y, Lambert, Amy J, Uitterlinden, Andre G, Franco, Oscar H, Hofer, Edith, Ginsburg, David, Hu, Bella, Keating, Brendan, Schick, Ursula M, Brody, Jennifer A, Li, Jun Z, Chen, Zhao, Zeller, Tanja, Guralnik, Jack M, Chasman, Daniel I, Peters, Luanne L, Kubo, Michiaki, Becker, Diane M, Li, Jin, Eiriksdottir, Gudny, Rotter, Jerome I, Levy, Daniel, Grossmann, Vera, Patel, Kushang V, Chen, Chien-Hsiun, Ridker, Paul M, Tang, Hua, Launer, Lenore J, Rice, Kenneth M, Li-Gao, Ruifang, Ferrucci, Luigi, Evans, Michelle K, Choudhuri, Avik, Trompouki, Eirini, Abraham, Brian J, Yang, Song, Takahashi, Atsushi, Kamatani, Yoichiro, Kooperberg, Charles, Harris, Tamara B, Jee, Sun Ha, Coresh, Josef, Tsai, Fuu-Jen, Longo, Dan L, Chen, Yuan-Tsong, Felix, Janine F, Yang, Qiong, Psaty, Bruce M, Boerwinkle, Eric, Becker, Lewis C, Mook-Kanamori, Dennis O, Wilson, James G, Gudnason, Vilmundur, O'Donnell, Christopher J, Dehghan, Abbas, Cupples, L Adrienne, Nalls, Michael A, Morris, Andrew P, Okada, Yukinori, Reiner, Alexander P, Zon, Leonard I and Ganesh, Santhi 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). pp. 51-63.

	Image 161026_Transethnic RBC CHARGE_Figure_1.jpg - Author Accepted Manuscript Download (608kB)
	Image 161026_Transethnic RBC CHARGE_Figure_2.jpg - Author Accepted Manuscript Download (392kB)
	Image 161026_Transethnic RBC CHARGE_Figure_3.jpg - Author Accepted Manuscript Download (217kB)
	Text 161026_Transethnic RBC CHARGE_Supplement.pdf - Author Accepted Manuscript Download (13MB)
	Text 161111_Transethnic RBC CHARGE_Manuscript_REVISION_AJHG_4.docx - Author Accepted Manuscript Download (205kB)
	Spreadsheet 161116_Transethnic RBC CHARGE_Supplemental Tables.xlsx - Author Accepted Manuscript Download (144kB)

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:	Article
Uncontrolled Keywords:	BioBank Japan Project, Erythrocytes, Animals, Zebrafish, Humans, RNA-Binding Proteins, Bayes Theorem, Erythropoiesis, Linkage Disequilibrium, Alleles, Africa, Europe, Female, Male, Genome-Wide Association Study, Ethnicity, Racial Groups, Asia, Eastern
Depositing User:	Symplectic Admin
Date Deposited:	20 Jan 2017 09:07
Last Modified:	13 Feb 2023 23:10
DOI:	10.1016/j.ajhg.2016.11.016
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3005279