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

Publication Type:

Journal Article

Authors:

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; 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, André 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; Ganesh, Santhi K

Source:

American journal of human genetics (2016)

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.