Literature DB >> 28017375

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

Frank J A van Rooij1, Rehan Qayyum2, Albert V Smith3, Yi Zhou4, Stella Trompet5, Toshiko Tanaka6, Margaux F Keller7, Li-Ching Chang8, Helena Schmidt9, Min-Lee Yang10, Ming-Huei Chen11, James Hayes12, Andrew D Johnson13, Lisa R Yanek2, Christian Mueller14, Leslie Lange15, James S Floyd16, Mohsen Ghanbari17, Alan B Zonderman18, J Wouter Jukema19, Albert Hofman20, Cornelia M van Duijn1, Karl C Desch21, Yasaman Saba9, Ayse B Ozel21, Beverly M Snively22, Jer-Yuarn Wu23, Reinhold Schmidt24, Myriam Fornage25, Robert J Klein12, Caroline S Fox13, Koichi Matsuda26, Naoyuki Kamatani27, Philipp S Wild28, David J Stott29, Ian Ford30, P Eline Slagboom31, Jaden Yang32, Audrey Y Chu33, Amy J Lambert34, André G Uitterlinden35, Oscar H Franco1, Edith Hofer36, David Ginsburg21, Bella Hu4, Brendan Keating37, Ursula M Schick38, Jennifer A Brody16, Jun Z Li21, Zhao Chen39, Tanja Zeller14, Jack M Guralnik40, Daniel I Chasman41, Luanne L Peters34, Michiaki Kubo42, Diane M Becker2, Jin Li43, Gudny Eiriksdottir44, Jerome I Rotter45, Daniel Levy13, Vera Grossmann46, Kushang V Patel18, Chien-Hsiun Chen23, Paul M Ridker47, Hua Tang48, Lenore J Launer49, Kenneth M Rice50, Ruifang Li-Gao51, Luigi Ferrucci6, Michelle K Evans52, Avik Choudhuri4, Eirini Trompouki53, Brian J Abraham54, Song Yang4, Atsushi Takahashi27, Yoichiro Kamatani27, Charles Kooperberg55, Tamara B Harris49, Sun Ha Jee56, Josef Coresh57, Fuu-Jen Tsai58, Dan L Longo59, Yuan-Tsong Chen8, Janine F Felix1, Qiong Yang60, Bruce M Psaty61, Eric Boerwinkle25, Lewis C Becker2, Dennis O Mook-Kanamori62, James G Wilson63, Vilmundur Gudnason3, Christopher J O'Donnell13, Abbas Dehghan64, L Adrienne Cupples60, Michael A Nalls7, Andrew P Morris65, Yukinori Okada66, Alexander P Reiner67, Leonard I Zon4, Santhi K Ganesh68.   

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.
Copyright © 2017 American Society of Human Genetics. All rights reserved.

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Year:  2016        PMID： 28017375      PMCID： PMC5223059          DOI： 10.1016/j.ajhg.2016.11.016

Source DB:  PubMed          Journal:  Am J Hum Genet        ISSN： 0002-9297            Impact factor:   11.043


  67 in total

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6.  The Netherlands Epidemiology of Obesity (NEO) study: study design and data collection.

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Journal:  Diabetes       Date:  2014-03-19       Impact factor: 9.461
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  23 in total

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2.  Harmonizing Genetic Ancestry and Self-identified Race/Ethnicity in Genome-wide Association Studies.

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Review 4.  Exploring the Activities of RBPMS Proteins in Myocardial Biology.

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6.  Cross-ancestry genome-wide meta-analysis of 61,047 cases and 947,237 controls identifies new susceptibility loci contributing to lung cancer.

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9.  An Asian-specific MPL genetic variant alters JAK-STAT signaling and influences platelet count in the population.

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10.  Genome-wide association studies identify 137 genetic loci for DNA methylation biomarkers of aging.

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