TY - JOUR
T1 - Genome-wide association analysis of red blood cell traits in African Americans
T2 - The cogent network
AU - Chen, Zhao
AU - Tang, Hua
AU - Qayyum, Rehan
AU - Schick, Ursula M.
AU - Nalls, Michael A.
AU - Handsaker, Rober
AU - Li, Jin
AU - Lu, Yingchang
AU - Yanek, Lisa R.
AU - Keating, Brendan
AU - Meng, Yan
AU - Van Rooij, Frank J.A.
AU - Okada, Yukinori
AU - Kubo, Michiaki
AU - Rasmussen-Torvik, Laura
AU - Keller, Margaux F.
AU - Lange, Leslie
AU - Evans, Michele
AU - Bottinger, Erwin P.
AU - Linderman, Michael D.
AU - Ruderfer, Douglas M.
AU - Hakonarson, Hakon
AU - Papanicolaou, George
AU - Zonderman, Alan B.
AU - Gottesman, Omri
AU - Thomson, Cynthia
AU - Ziv, Elad
AU - Singleton, Andrew B.
AU - Loos, Ruth J.F.
AU - Sleiman, Patrick M.A.
AU - Ganesh, Santhi
AU - McCarroll, Steven
AU - Becker, Diane M.
AU - Wilson, James G.
AU - Lettre, Guillaume
AU - Reiner, Alexander P.
N1 - Funding Information:
GeneSTAR: this research was supported by the National Heart, Lung and Blood Institute (NHLBI) through the PROGENI (U01 HL72518) and STAMPEED (R01 HL087698-01) consortia. Additional support was provided by grants from the NIH/National Institute of Nursing Research (R01 NR08153), and the NIH/National Center for Research Resources (M01-RR000052) to the Johns Hopkins General Clinical Research Center.
Funding Information:
AGES: the Age, Gene/Environment Susceptibility Reykjavik Study is funded by NIH contract N01-AG-12100, the NIA Intramural Research Program, Hjartavernd (the Icelandic Heart Association) and the Althingi (the Icelandic Parliament).
Funding Information:
We thank all the children who donated blood samples for genetic research purpose. The CHOP study was funded by the Institute Development Funds to the Center for Applied Genomics at the Children’s Hospital of Philadelphia and an Adele S. and Daniel S. Kubert Estate gift to the Center for Applied Genomics.
Funding Information:
Rotterdam: Rotterdam Study GWAS database of the Rotterdam Study was funded through the Netherlands Organization of Scientific Research NWO (no. 175.010.2005.011, 911.03.012) and the Research Institute for Diseases in the Elderly (RIDE). This study was supported by the Netherlands Genomics Initiative (NGI)/NWO project number 050 060 810 (Netherlands Consortium for Healthy Ageing). We thank Dr Michael Moorhouse, Pascal Arp, Mila Jhamai, Marijn Verkerk and Sander Bervoets for their help in creating the genetic database. We thank the laboratory technicians Jeannette M Vergeer—Drop, Bernadette H M van Ast—Copier, Andy A L J van Oosterhout, Sue Ellen Mauricia, Andrea J M Vermeij—Verdoold, Els Halbmeijer—van der Plas, Debby M S Lont and Hasna Kariouh for their help in phenotype assessment. The Rotterdam Study is supported by the Erasmus Medical Center and Erasmus University, Rotterdam; the Netherlands organization for scientific research (NWO), the Netherlands Organization for the Health Research and Development (ZonMw), the Research Institute for Diseases in the Elderly (RIDE), the Netherlands Heart Foundation, the Ministry of Education, Culture and Science, the Ministry of Health, Welfare and Sports, the European Commission (DG XII) and the Municipality of Rotterdam.
Funding Information:
RIKEN: we would like to thank all the staff of the Laboratory for Statistical Analysis at RIKEN for their technical assistance. The BioBank Japan Project was supported by Ministry of Education, Culture, Sports, Science and Technology, Japan.
Funding Information:
WHI: the WHI program is funded by the National Heart, Lung and Blood Institute, National Institutes of Health, US Department of Health and Human Services through contracts N01WH22110, 24152, 32100–2, 32105–6, 32108–9, 32111–13, 32115, 32118–32119, 32122, 42107–26, 42129–32 and 44221.
Funding Information:
Health ABC: this research was supported by NIA contracts N01AG62101, N01AG62103 and N01AG62106. The GWAS was funded by NIA grant 1R01AG032098-01A1 to Wake Forest University Health Sciences and genotyping services were provided by the Center for Inherited Disease Research (CIDR). CIDR is fully funded through a federal contract from the National Institutes of Health to The Johns Hopkins University, contract number HHSN268200782096C. This research was supported in part by the Intramural Research Program of the NIH, National Institute on Aging.
Funding Information:
Framingham: the National Heart, Lung and Blood Institute’s Framingham Heart Study is a joint project of the National Institutes of Health and Boston University School of Medicine and was supported bythe National Heart, Lung, and Blood Institute’s Framingham Heart Study (contract No. N01-HC-25195) and its contract with Affymetrix, Inc. for genotyping services (contract No. N02-HL-6-4278). Analyses reflect the efforts and resource development from the Framing-ham Heart Study investigators participating in the SNP Health Association Resource (SHARe) project. A portion of this research was conducted using the Linux Cluster for Genetic Analysis (LinGA-II) funded by the Robert Dawson Evans Endowment of the Department of Medicine at Boston University School of Medicine and Boston Medical Center.
Funding Information:
InChianti: the InChianti Study was supported as a “targeted project” (ICS 110.1RS97.71) by the Italian Ministry of Health, by the US National Institute on Aging (Contracts N01-AG-916413, N01-AG-821336, 263 MD 9164 13 and 263 MD 821336) and in part by the Intramural Research Program, National Institute on Aging, National Institutes of Health, USA.
Funding Information:
Healthy Aging in Neighborhoods of Diversity across the Life Span Study (HANDLS): this research was supported by the Intramural Research Program of the NIH, National Institute on Aging and the National Center on Minority Health and Health Disparities (intramural project Z01-AG000513 and human subjects protocol 2009-149). Data analyses for the HANDLS study utilized the high-performance computational capabilities of the Biowulf Linux cluster at the National Institutes of Health, Bethesda, MD, USA (http://biowulf.nih.gov).
Funding Information:
The Mount Sinai IPM Biobank Program is supported by The Andrea and Charles Bronfman Philanthropies.
PY - 2013/6
Y1 - 2013/6
N2 - Laboratory red blood cell (RBC) measurements are clinically important, heritable and differ among ethnic groups. To identify genetic variants that contribute to RBC phenotypes in African Americans (AAs), we conducted a genome-wide association study in up to ~16 500 AAs. The alpha-globin locus on chromosome 16pter [lead SNP rs13335629 in ITFG3 gene; P < 1E-13 for hemoglobin (Hgb), RBC count, mean corpuscular volume (MCV), MCH and MCHC] and the G6PD locus on Xq28 [lead SNP rs1050828; P < 1E - 13 for Hgb, hematocrit (Hct), MCV, RBC count and red cell distribution width (RDW)] were each associated with multiple RBC traits. At the alpha-globin region, both the common African 3.7 kb deletion and common single nucleotide polymorphisms (SNPs) appear to contribute independently to RBC phenotypes among AAs. In the 2p21 region, we identified a novel variant of PRKCE distinctly associated with Hct in AAs. In a genome-wide admixture mapping scan, local European ancestry at the 6p22 region containing HFE and LRRC16A was associated with higher Hgb. LRRC16A has been previously associated with the platelet count and mean platelet volume in AAs, but not with Hgb. Finally, we extended to AAs the findings of association of erythrocyte traits with several loci previously reported in Europeans and/or Asians, including CD164 and HBS1L-MYB. In summary, this large-scale genome-wide analysis in AAs has extended the importance of several RBC-associated genetic loci to AAs and identified allelic heterogeneity and pleiotropy at several previously known genetic loci associated with blood cell traits in AAs.
AB - Laboratory red blood cell (RBC) measurements are clinically important, heritable and differ among ethnic groups. To identify genetic variants that contribute to RBC phenotypes in African Americans (AAs), we conducted a genome-wide association study in up to ~16 500 AAs. The alpha-globin locus on chromosome 16pter [lead SNP rs13335629 in ITFG3 gene; P < 1E-13 for hemoglobin (Hgb), RBC count, mean corpuscular volume (MCV), MCH and MCHC] and the G6PD locus on Xq28 [lead SNP rs1050828; P < 1E - 13 for Hgb, hematocrit (Hct), MCV, RBC count and red cell distribution width (RDW)] were each associated with multiple RBC traits. At the alpha-globin region, both the common African 3.7 kb deletion and common single nucleotide polymorphisms (SNPs) appear to contribute independently to RBC phenotypes among AAs. In the 2p21 region, we identified a novel variant of PRKCE distinctly associated with Hct in AAs. In a genome-wide admixture mapping scan, local European ancestry at the 6p22 region containing HFE and LRRC16A was associated with higher Hgb. LRRC16A has been previously associated with the platelet count and mean platelet volume in AAs, but not with Hgb. Finally, we extended to AAs the findings of association of erythrocyte traits with several loci previously reported in Europeans and/or Asians, including CD164 and HBS1L-MYB. In summary, this large-scale genome-wide analysis in AAs has extended the importance of several RBC-associated genetic loci to AAs and identified allelic heterogeneity and pleiotropy at several previously known genetic loci associated with blood cell traits in AAs.
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U2 - 10.1093/hmg/ddt087
DO - 10.1093/hmg/ddt087
M3 - Article
C2 - 23446634
AN - SCOPUS:84878476011
SN - 0964-6906
VL - 22
SP - 2529
EP - 2538
JO - Human molecular genetics
JF - Human molecular genetics
IS - 12
ER -