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RESEARCH PRODUCT

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

Dennis O. Mook-kanamoriDennis O. Mook-kanamoriRehan QayyumLisa R. YanekLuigi FerrucciMin-lee YangDavid J. StottP. Eline SlagboomJin LiSanthi K. GaneshVera GrossmannMyriam FornageEdith HoferLewis C. BeckerLenore J. LaunerAlbert V. SmithBrendan J. KeatingFrank J. A. Van RooijAlbert HofmanAlbert HofmanJun LiMichiaki KuboChristian MuellerStella TrompetQiong YangQiong YangAndrew D. JohnsonZhao ChenRobert J. KleinLuanne L. PetersAmy J. LambertReinhold SchmidtEirini TrompoukiEirini TrompoukiKenneth RiceJosef CoreshNaoyuki KamataniVilmundur GudnasonLeslie A. LangeBrian J. AbrahamUrsula M. SchickUrsula M. SchickEric BoerwinkleLeonard I. ZonBruce M. PsatyBruce M. PsatyDiane M. BeckerDavid GinsburgGudny EiriksdottirBella HuMohsen GhanbariMohsen GhanbariDan L. LongoCornelia M. Van DuijnOscar H. FrancoBeverly M. SnivelyMargaux F. KellerL. Adrienne CupplesL. Adrienne CupplesYukinori OkadaJames E. HayesIan FordJack M. GuralnikKoichi MatsudaJ. Wouter JukemaAndré G. UitterlindenYoichiro KamataniHelena SchmidtJames G. WilsonMichelle K. EvansTanja ZellerAlan B. ZondermanFuu Jen TsaiYasaman SabaDaniel LevyPhilipp S. WildPaul M. RidkerJaden YangJer-yuarn WuJer-yuarn WuJanine F. FelixMike A. NallsChristopher J. O'donnellKarl C. DeschCaroline S. FoxJennifer A. BrodyAlexander P. ReinerAlexander P. ReinerAvik ChoudhuriAyse Bilge OzelAbbas DehghanAbbas DehghanAndrew P. MorrisAndrew P. MorrisRuifang Li-gaoDaniel I. ChasmanTamara B. HarrisAudrey Y. ChuToshiko TanakaCharles KooperbergHua TangSong YangYi ZhouSun Ha JeeKushang V. PatelJames S. FloydAtsushi TakahashiYuan-tsong ChenMing-huei ChenMing-huei ChenJerome I. RotterLi Ching ChangChien-hsiun ChenChien-hsiun Chen

subject

0301 basic medicineMaleLinkage disequilibriumAsiaErythrocytesGenome-wide association studyLocus (genetics)RBPMS030105 genetics & heredityBiologyEasternGenomeMedical and Health SciencesArticleLinkage Disequilibrium03 medical and health sciencesGeneticsEthnicityAnimalsHumansErythropoiesisAlleleGenetics (clinical)Loss functionAllelesZebrafishGenetic associationGeneticsGenetics & HeredityAsia EasternHuman GenomeRacial GroupsRNA-Binding ProteinsBioBank Japan ProjectBayes TheoremHematologyBiological SciencesR13. Good healthEurope030104 developmental biologyAfricaFemaleGenome-Wide Association Study

description

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.

yearjournalcountryeditionlanguage
2017-01-05
10.1016/j.ajhg.2016.11.016https://doi.org/10.1016/j.ajhg.2016.11.016