Title

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

Authors

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

Document Type

Article

Publication Date

1-5-2017

JAX Source

Am J Hum Genet 2017 Jan 5; 100(1):51-63

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. Am J Hum Genet 2017 Jan 5; 100(1):51-63.