Genome-wide Trans-ethnic Meta-analysis Identifies Seven Genetic Loci Influencing Erythrocyte Traits and a Role for RBPMS in Erythropoiesis
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Genome-wide Trans-ethnic Meta-analysis Identifies Seven Genetic Loci Influencing Erythrocyte Traits and a Role for RBPMS in Erythropoiesis. / 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; BioBank Japan Project.
In: AM J HUM GENET, Vol. 100, No. 1, 05.01.2017, p. 51-63.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Genome-wide Trans-ethnic Meta-analysis Identifies Seven Genetic Loci Influencing Erythrocyte Traits and a Role for RBPMS in Erythropoiesis
AU - van Rooij, Frank J A
AU - Qayyum, Rehan
AU - Smith, Albert V
AU - Zhou, Yi
AU - Trompet, Stella
AU - Tanaka, Toshiko
AU - Keller, Margaux F
AU - Chang, Li-Ching
AU - Schmidt, Helena
AU - Yang, Min-Lee
AU - Chen, Ming-Huei
AU - Hayes, James
AU - Johnson, Andrew D
AU - Yanek, Lisa R
AU - Mueller, Christian
AU - Lange, Leslie
AU - Floyd, James S
AU - Ghanbari, Mohsen
AU - Zonderman, Alan B
AU - Jukema, J Wouter
AU - Hofman, Albert
AU - van Duijn, Cornelia M
AU - Desch, Karl C
AU - Saba, Yasaman
AU - Ozel, Ayse B
AU - Snively, Beverly M
AU - Wu, Jer-Yuarn
AU - Schmidt, Reinhold
AU - Fornage, Myriam
AU - Klein, Robert J
AU - Fox, Caroline S
AU - Matsuda, Koichi
AU - Kamatani, Naoyuki
AU - Wild, Philipp S
AU - Stott, David J
AU - Ford, Ian
AU - Slagboom, P Eline
AU - Yang, Jaden
AU - Chu, Audrey Y
AU - Lambert, Amy J
AU - Uitterlinden, André G
AU - Franco, Oscar H
AU - Hofer, Edith
AU - Ginsburg, David
AU - Hu, Bella
AU - Keating, Brendan
AU - Schick, Ursula M
AU - Brody, Jennifer A
AU - Li, Jun Z
AU - Chen, Zhao
AU - Zeller, Tanja
AU - Guralnik, Jack M
AU - Chasman, Daniel I
AU - Peters, Luanne L
AU - Kubo, Michiaki
AU - Becker, Diane M
AU - Li, Jin
AU - Eiriksdottir, Gudny
AU - Rotter, Jerome I
AU - Levy, Daniel
AU - Grossmann, Vera
AU - Patel, Kushang V
AU - Chen, Chien-Hsiun
AU - Ridker, Paul M
AU - Tang, Hua
AU - Launer, Lenore J
AU - Rice, Kenneth M
AU - Li-Gao, Ruifang
AU - Ferrucci, Luigi
AU - Evans, Michelle K
AU - Choudhuri, Avik
AU - Trompouki, Eirini
AU - Abraham, Brian J
AU - Yang, Song
AU - Takahashi, Atsushi
AU - Kamatani, Yoichiro
AU - Kooperberg, Charles
AU - Harris, Tamara B
AU - Jee, Sun Ha
AU - Coresh, Josef
AU - Tsai, Fuu-Jen
AU - Longo, Dan L
AU - Chen, Yuan-Tsong
AU - Felix, Janine F
AU - Yang, Qiong
AU - Psaty, Bruce M
AU - Boerwinkle, Eric
AU - Becker, Lewis C
AU - Mook-Kanamori, Dennis O
AU - Wilson, James G
AU - Gudnason, Vilmundur
AU - O'Donnell, Christopher J
AU - Dehghan, Abbas
AU - Cupples, L Adrienne
AU - Nalls, Michael A
AU - Morris, Andrew P
AU - Okada, Yukinori
AU - Reiner, Alexander P
AU - Zon, Leonard I
AU - Ganesh, Santhi K
AU - BioBank Japan Project
N1 - Copyright © 2017 American Society of Human Genetics. All rights reserved.
PY - 2017/1/5
Y1 - 2017/1/5
N2 - 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.
AB - 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.
KW - Africa/ethnology
KW - Alleles
KW - Animals
KW - Bayes Theorem
KW - Continental Population Groups/genetics
KW - Erythrocytes/metabolism
KW - Erythropoiesis/genetics
KW - Ethnic Groups/genetics
KW - Europe/ethnology
KW - Far East/ethnology
KW - Female
KW - Genome-Wide Association Study
KW - Humans
KW - Linkage Disequilibrium
KW - Male
KW - RNA-Binding Proteins/genetics
KW - Zebrafish/genetics
U2 - 10.1016/j.ajhg.2016.11.016
DO - 10.1016/j.ajhg.2016.11.016
M3 - SCORING: Journal article
C2 - 28017375
VL - 100
SP - 51
EP - 63
JO - AM J HUM GENET
JF - AM J HUM GENET
SN - 0002-9297
IS - 1
ER -