Multiple loci influence erythrocyte phenotypes in the CHARGE Consortium

Santhi Ganesh and colleagues report meta-analyses of genome-wide association studies of six erythrocyte traits within the CHARGE consortium, with replication in cohorts of the HaemGen consortium. They report 23 loci associated with a range of clinically relevant red blood cell traits. Measurements o...

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Veröffentlicht in:	Nature genetics Jg. 41; H. 11; S. 1191 - 1198
Hauptverfasser:	Ganesh, Santhi K, Zakai, Neil A, van Rooij, Frank J A, Soranzo, Nicole, Smith, Albert V, Nalls, Michael A, Chen, Ming-Huei, Kottgen, Anna, Glazer, Nicole L, Dehghan, Abbas, Kuhnel, Brigitte, Aspelund, Thor, Yang, Qiong, Tanaka, Toshiko, Jaffe, Andrew, Bis, Joshua C M, Verwoert, Germaine C, Teumer, Alexander, Fox, Caroline S, Guralnik, Jack M, Ehret, Georg B, Rice, Kenneth, Felix, Janine F, Rendon, Augusto, Eiriksdottir, Gudny, Levy, Daniel, Patel, Kushang V, Boerwinkle, Eric, Rotter, Jerome I, Hofman, Albert, Sambrook, Jennifer G, Hernandez, Dena G, Zheng, Gang, Bandinelli, Stefania, Singleton, Andrew B, Coresh, Josef, Lumley, Thomas, Uitterlinden, André G, vanGils, Janine M, Launer, Lenore J, Cupples, L Adrienne, Oostra, Ben A, Zwaginga, Jaap-Jan, Ouwehand, Willem H, Thein, Swee-Lay, Meisinger, Christa, Deloukas, Panos, Nauck, Matthias, Spector, Tim D, Gieger, Christian, Gudnason, Vilmundur, van Duijn, Cornelia M, Psaty, Bruce M, Ferrucci, Luigi, Chakravarti, Aravinda, Greinacher, Andreas, O'Donnell, Christopher J, Witteman, Jacqueline C M, Furth, Susan, Cushman, Mary, Harris, Tamara B, Lin, Jing-Ping
Format:	Journal Article
Sprache:	Englisch
Veröffentlicht:	New York Nature Publishing Group US 01.11.2009 Nature Publishing Group
Schlagworte:	Agriculture Animal Genetics and Genomics Biological and medical sciences Biomedical and Life Sciences Biomedicine Blood diseases Blood pressure Blood Pressure - genetics Cancer Research Cell Line Clinical medicine Cohort Studies Data analysis Endothelial Cells - metabolism Erythrocytes Erythrocytes - metabolism Fundamental and applied biological sciences. Psychology Gene Expression Gene Function Genetic aspects Genetic disorders Genetics of eukaryotes. Biological and molecular evolution Genome, Human Genome-Wide Association Study Genotype & phenotype Hemoglobin Human Genetics Humans Hypertension - genetics Inflation Meta-analysis Phenotype Physiological aspects Polymorphism, Single Nucleotide Quantitative Trait Loci Sample size United States United Kingdom Netherlands Locus Phenotype
ISSN:	1061-4036, 1546-1718, 1546-1718
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Zusammenfassung:	Santhi Ganesh and colleagues report meta-analyses of genome-wide association studies of six erythrocyte traits within the CHARGE consortium, with replication in cohorts of the HaemGen consortium. They report 23 loci associated with a range of clinically relevant red blood cell traits. Measurements of erythrocytes within the blood are important clinical traits and can indicate various hematological disorders. We report here genome-wide association studies (GWAS) for six erythrocyte traits, including hemoglobin concentration (Hb), hematocrit (Hct), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC) and red blood cell count (RBC). We performed an initial GWAS in cohorts of the CHARGE Consortium totaling 24,167 individuals of European ancestry and replication in additional independent cohorts of the HaemGen Consortium totaling 9,456 individuals. We identified 23 loci significantly associated with these traits in a meta-analysis of the discovery and replication cohorts (combined P values ranging from 5 × 10 −8 to 7 × 10 −86 ). Our findings include loci previously associated with these traits ( HBS1L-MYB , HFE , TMPRSS6 , TFR2 , SPTA1 ) as well as new associations ( EPO , TFRC , SH2B3 and 15 other loci). This study has identified new determinants of erythrocyte traits, offering insight into common variants underlying variation in erythrocyte measures.
Bibliographie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 CHS: Study design and phenotype collection, BMP, JIR, MC, NAZ, NLG; Genotyping, JIR; data analysis, NLG, TL; manuscript preparation, NAZ; manuscript revisions BMP, JCB, KR, JLR, MC, NAZ, NLG, TL FHS: Study design and phenotype collection, MHC, QY, CSF, DL, LAC, CJO, JPL; Genotyping,; data analysis, MHC, QY, JPL; manuscript preparation, MHC, CJO, JPL; manuscript revisions, MHC, QY, CSF, DL, LAC, CJO, JPL. HaemGen ARIC: Study design and phenotype collection, EB, JC, SF, AC; Genotyping, EB, AC; data analysis, SKG, AK, AC, AG, GBE; manuscript preparation, SKG, SF; manuscript revisions, SKG, AC, EB, JC, AK, SF. Authors indicated by an asterisk (*) contributed equally as junior authors SHIP: Study design and phenotype collection, MN, AG; data analysis, AT Authors indicated by a caret (^) contributed equally as senior authors TwinsUK: Study design and phenotype collection, TDS, SLT, PD; data analysis, NS; manuscript preparation NS, manuscript revisions, NS KORA: Study design and phenotype collection, CM, CG; data analysis, CG, BK; manuscript preparation CG, manuscript revisions, CG Gene expression: AR, JJZ, JMvG Rotterdam: Study design and phenotype collection, FJAR, AH, AGU, BAO, CMD, JCMW; Genotyping, AGU; data analysis, FJAR, JFF, AD, GCV; manuscript preparation, FJAR, JFF, CMD; manuscript revisions FJAR, JFF, AD, GCV, AH, AGU, BAO, CMD, JCMW AGES: Study design and phenotype collection, TBH,VG,LJL; Genotyping,; data analysis, AVS, MAN,TA; manuscript preparation, MAN, NS; manuscript revisions, TBH,VG,LJL, AVS, ABS, DGH, MAN InCHIANTI: Study design and phenotype collection, LF,JMG,SB; Genotyping, ; data analysis, MAN,TT; manuscript preparation, MAN; Manuscript revisions, LF, JMG, SB, KVP, ABS, DGH, MAN, TT UKBS1: Study design and phenotype collection, WHO, JGS; data analysis, NS; manuscript preparation NS, AR, manuscript revisions, NS, AR Author Contributions CHARGE Genotyping, AR, JJZ, JMvG
ISSN:	1061-4036 1546-1718 1546-1718
DOI:	10.1038/ng.466