Genome-wide Trans-ethnic Meta-analysis Identifies Seven Genetic Loci Influencing Erythrocyte Traits and a Role for RBPMS in Erythropoiesis.
| Citation | . “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, pp. 51-63. |
| Center | UCSD-UCLA |
| Author | Frank J A van Rooij, Rehan Qayyum, Albert Smith V, 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, 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, Eline Slagboom, Jaden Yang, Audrey Y Chu, Amy J Lambert, 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, Michiaki Kubo, Diane M Becker, Jin Li, Gudny Eiriksdottir, Jerome I Rotter, Daniel Levy, Vera Grossmann, Kushang Patel V, Chien-Hsiun Chen, BioBank Japan Project, 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, Adrienne Cupples, Michael A Nalls, Andrew P Morris, Yukinori Okada, Alexander P Reiner, Leonard I Zon, Santhi K Ganesh |
| 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. |
| Year of Publication |
2017
|
| Journal |
American journal of human genetics
|
| Volume |
100
|
| Issue |
1
|
| Number of Pages |
51-63
|
| Date Published |
01/2017
|
| ISSN Number |
1537-6605
|
| DOI |
10.1016/j.ajhg.2016.11.016
|
| Alternate Journal |
Am. J. Hum. Genet.
|
| PMID |
28017375
|
| PMCID |
PMC5223059
|
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