04812nas a2201345 4500008004100000022001400041245014400055210006900199260001600268300001000284490000800294520106400302100002601366700001801392700002101410700001301431700002001444700002001464700002301484700002001507700002001527700001801547700002001565700001701585700002301602700001901625700002301644700001801667700002001685700002101705700002301726700001901749700001901768700002301787700001901810700001801829700001801847700002401865700001801889700002201907700002001929700002101949700002101970700002001991700002202011700002102033700002002054700001402074700002002088700001602108700001902124700002002143700002802163700002102191700001702212700002002229700001402249700002102263700002202284700002302306700001502329700001502344700001802359700002202377700002302399700002202422700001902444700002102463700001202484700002402496700002202520700001702542700002002559700002202579700002202601700002002623700001402643700002202657700002102679700002002700700002002720700002302740700002002763700002202783700002202805700001502827700002302842700002302865700002402888700002202912700001702934700001802951700001802969700001802987700002103005700002103026700001603047700002003063700002103083700002103104700002903125700002103154700002403175700003003199700001903229700002503248700002203273700002203295700002003317700002503337700002003362700002203382710002603404856003603430 2017 eng d a1537-660500aGenome-wide Trans-ethnic Meta-analysis Identifies Seven Genetic Loci Influencing Erythrocyte Traits and a Role for RBPMS in Erythropoiesis.0 aGenomewide Transethnic Metaanalysis Identifies Seven Genetic Loc c2017 Jan 05 a51-630 v1003 a
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.
1 avan Rooij, Frank, J A1 aQayyum, Rehan1 aSmith, Albert, V1 aZhou, Yi1 aTrompet, Stella1 aTanaka, Toshiko1 aKeller, Margaux, F1 aChang, Li-Ching1 aSchmidt, Helena1 aYang, Min-Lee1 aChen, Ming-Huei1 aHayes, James1 aJohnson, Andrew, D1 aYanek, Lisa, R1 aMueller, Christian1 aLange, Leslie1 aFloyd, James, S1 aGhanbari, Mohsen1 aZonderman, Alan, B1 aJukema, Wouter1 aHofman, Albert1 aDuijn, Cornelia, M1 aDesch, Karl, C1 aSaba, Yasaman1 aOzel, Ayse, B1 aSnively, Beverly, M1 aWu, Jer-Yuarn1 aSchmidt, Reinhold1 aFornage, Myriam1 aKlein, Robert, J1 aFox, Caroline, S1 aMatsuda, Koichi1 aKamatani, Naoyuki1 aWild, Philipp, S1 aStott, David, J1 aFord, Ian1 aSlagboom, Eline1 aYang, Jaden1 aChu, Audrey, Y1 aLambert, Amy, J1 aUitterlinden, André, G1 aFranco, Oscar, H1 aHofer, Edith1 aGinsburg, David1 aHu, Bella1 aKeating, Brendan1 aSchick, Ursula, M1 aBrody, Jennifer, A1 aLi, Jun, Z1 aChen, Zhao1 aZeller, Tanja1 aGuralnik, Jack, M1 aChasman, Daniel, I1 aPeters, Luanne, L1 aKubo, Michiaki1 aBecker, Diane, M1 aLi, Jin1 aEiriksdottir, Gudny1 aRotter, Jerome, I1 aLevy, Daniel1 aGrossmann, Vera1 aPatel, Kushang, V1 aChen, Chien-Hsiun1 aRidker, Paul, M1 aTang, Hua1 aLauner, Lenore, J1 aRice, Kenneth, M1 aLi-Gao, Ruifang1 aFerrucci, Luigi1 aEvans, Michelle, K1 aChoudhuri, Avik1 aTrompouki, Eirini1 aAbraham, Brian, J1 aYang, Song1 aTakahashi, Atsushi1 aKamatani, Yoichiro1 aKooperberg, Charles1 aHarris, Tamara, B1 aJee, Sun, Ha1 aCoresh, Josef1 aTsai, Fuu-Jen1 aLongo, Dan, L1 aChen, Yuan-Tsong1 aFelix, Janine, F1 aYang, Qiong1 aPsaty, Bruce, M1 aBoerwinkle, Eric1 aBecker, Lewis, C1 aMook-Kanamori, Dennis, O1 aWilson, James, G1 aGudnason, Vilmundur1 aO'Donnell, Christopher, J1 aDehghan, Abbas1 aCupples, Adrienne, L1 aNalls, Michael, A1 aMorris, Andrew, P1 aOkada, Yukinori1 aReiner, Alexander, P1 aZon, Leonard, I1 aGanesh, Santhi, K1 aBioBank Japan Project uhttps://chs-nhlbi.org/node/7364