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

详细信息    查看全文

• 作者：Frank J.A. van Rooij¹ ; Rehan Qayyum² ; Albert V. Smith³ ; ⁴ ; Yi Zhou⁵ ; ⁶ ; Stella Trompet⁷ ; ⁸ ; Toshiko Tanaka⁹ ; Margaux F. Keller¹⁰ ; Li-Ching Chang¹¹ ; Helena Schmidt¹² ; Min-Lee Yang¹³ ; Ming-Huei Chen¹⁴ ; ¹⁵ ; James Hayes¹⁶ ; Andrew D. Johnson¹⁵ ; Lisa R. Yanek² ; Christian Mueller¹⁷ ; ⁴⁶ ; Leslie Lange¹⁸ ; James S. Floyd¹⁹ ; Mohsen Ghanbari¹ ; ²⁰ ; Alan B. Zonderman²¹ ; J. Wouter Jukema⁷ ; Albert Hofman¹ ; ²² ; Cornelia M. van Duijn¹ ; Karl C. Desch²³ ; Yasaman Saba¹² ; Ayse B. Ozel²³ ; Beverly M. Snively²⁴ ; Jer-Yuarn Wu¹¹ ; ²⁵ ; Reinhold Schmidt²⁶ ; Myriam Fornage²⁷ ; Robert J. Klein¹⁶ ; Caroline S. Fox¹⁵ ; Koichi Matsuda²⁸ ; Naoyuki Kamatani²⁹ ; Philipp S. Wild³⁰ ; ³¹ ; ³² ; David J. Stott³³ ; Ian Ford³⁴ ; P. Eline Slagboom³⁵ ; Jaden Yang³⁶ ; Audrey Y. Chu³⁷ ; Amy J. Lambert³⁸ ; André ; G. Uitterlinden¹ ; ³⁹ ; Oscar H. Franco¹ ; Edith Hofer²⁶ ; ⁴⁰ ; David Ginsburg²³ ; Bella Hu⁵ ; ⁶ ; Brendan Keating⁴¹ ; ⁴² ; Ursula M. Schick⁴³ ; ⁴⁴ ; Jennifer A. Brody¹⁹ ; Jun Z. Li²³ ; Zhao Chen⁴⁵
• 刊名：The American Journal of Human Genetics
• 出版年：2017
• 出版时间：5 January 2017
• 年：2017
• 卷：100
• 期：1
• 页码：51-63
• 全文大小：1316 K
• 卷排序：100

文摘

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.