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

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.

SUBMITTER: van Rooij FJA 

PROVIDER: S-EPMC5223059 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature

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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 FJA   Qayyum Rehan R   Smith Albert V AV   Zhou Yi Y   Trompet Stella S   Tanaka Toshiko T   Keller Margaux F MF   Chang Li-Ching LC   Schmidt Helena H   Yang Min-Lee ML   Chen Ming-Huei MH   Hayes James J   Johnson Andrew D AD   Yanek Lisa R LR   Mueller Christian C   Lange Leslie L   Floyd James S JS   Ghanbari Mohsen M   Zonderman Alan B AB   Jukema J Wouter JW   Hofman Albert A   van Duijn Cornelia M CM   Desch Karl C KC   Saba Yasaman Y   Ozel Ayse B AB   Snively Beverly M BM   Wu Jer-Yuarn JY   Schmidt Reinhold R   Fornage Myriam M   Klein Robert J RJ   Fox Caroline S CS   Matsuda Koichi K   Kamatani Naoyuki N   Wild Philipp S PS   Stott David J DJ   Ford Ian I   Slagboom P Eline PE   Yang Jaden J   Chu Audrey Y AY   Lambert Amy J AJ   Uitterlinden André G AG   Franco Oscar H OH   Hofer Edith E   Ginsburg David D   Hu Bella B   Keating Brendan B   Schick Ursula M UM   Brody Jennifer A JA   Li Jun Z JZ   Chen Zhao Z   Zeller Tanja T   Guralnik Jack M JM   Chasman Daniel I DI   Peters Luanne L LL   Kubo Michiaki M   Becker Diane M DM   Li Jin J   Eiriksdottir Gudny G   Rotter Jerome I JI   Levy Daniel D   Grossmann Vera V   Patel Kushang V KV   Chen Chien-Hsiun CH   Ridker Paul M PM   Tang Hua H   Launer Lenore J LJ   Rice Kenneth M KM   Li-Gao Ruifang R   Ferrucci Luigi L   Evans Michelle K MK   Choudhuri Avik A   Trompouki Eirini E   Abraham Brian J BJ   Yang Song S   Takahashi Atsushi A   Kamatani Yoichiro Y   Kooperberg Charles C   Harris Tamara B TB   Jee Sun Ha SH   Coresh Josef J   Tsai Fuu-Jen FJ   Longo Dan L DL   Chen Yuan-Tsong YT   Felix Janine F JF   Yang Qiong Q   Psaty Bruce M BM   Boerwinkle Eric E   Becker Lewis C LC   Mook-Kanamori Dennis O DO   Wilson James G JG   Gudnason Vilmundur V   O'Donnell Christopher J CJ   Dehghan Abbas A   Cupples L Adrienne LA   Nalls Michael A MA   Morris Andrew P AP   Okada Yukinori Y   Reiner Alexander P AP   Zon Leonard I LI   Ganesh Santhi K SK  

American journal of human genetics 20161222 1

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) associate  ...[more]

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