Genome-wide association analysis of red blood cell traits in African Americans: the COGENT Network

被引：47

作者：

Chen, Zhao ^{[1
]}

Tang, Hua ^{[3
,4
]}

Qayyum, Rehan ^{[5
]}

Schick, Ursula M. ^{[6
]}

Nalls, Michael A. ^{[7
]}

Handsaker, Robert ^{[8
]}

Li, Jin ^{[9
]}

Lu, Yingchang ^{[11
]}

Yanek, Lisa R. ^{[16
]}

Keating, Brendan ^{[17
]}

Meng, Yan ^{[19
]}

van Rooij, Frank J. A. ^{[20
]}

Okada, Yukinori ^{[19
,21
,22
]}

Kubo, Michiaki ^{[23
]}

Rasmussen-Torvik, Laura ^{[24
]}

Keller, Margaux F. ^{[25
]}

Lange, Leslie ^{[26
]}

Evans, Michele ^{[27
]}

Bottinger, Erwin P. ^{[12
]}

Linderman, Michael D. ^{[13
]}

Ruderfer, Douglas M. ^{[14
]}

Hakonarson, Hakon ^{[9
,10
,18
]}

Papanicolaou, George ^{[28
]}

Zonderman, Alan B. ^{[29
]}

Gottesman, Omri ^{[12
]}

Thomson, Cynthia ^{[2
]}

Ziv, Elad ^{[30
]}

Singleton, Andrew B. ^{[25
]}

Loos, Ruth J. F. ^{[15
]}

Sleiman, Patrick M. A. ^{[9
,10
,18
]}

Ganesh, Santhi ^{[31
]}

McCarroll, Steven ^{[32
,33
]}

Becker, Diane M. ^{[5
]}

Wilson, James G. ^{[34
]}

Lettre, Guillaume ^{[35
]}

Reiner, Alexander P. ^{[6
,36
]}

机构：

[1] Univ Arizona, Mel & Enid Zuckerman Coll Publ Hlth, Div Epidemiol & Biostat, Tucson, AZ 85724 USA

[2] Univ Arizona, Mel & Enid Zuckerman Coll Publ Hlth, Div Nutr, Tucson, AZ 85724 USA

[3] Stanford Univ, Dept Stat, Stanford, CA 94305 USA

[4] Stanford Univ, Dept Genet, Stanford, CA 94305 USA

[5] Johns Hopkins Sch Med, Div Gen Internal Med, GeneSTAR Res Program, Baltimore, MD 21287 USA

[6] Univ Washington, Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98195 USA

[7] NIA, Mol Genet Sect, Neurogenet Lab, Bethesda, MD 20892 USA

[8] Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA 02141 USA

[9] Childrens Hosp Philadelphia, Abramson Res Ctr, Ctr Appl Genom, Philadelphia, PA 19104 USA

[10] Childrens Hosp Philadelphia, Div Human Genet, Philadelphia, PA 19104 USA

[11] Mt Sinai Sch Med, Charles Bronfman Inst Personalized Med, Genet Obes & Related Metab Traits Program, New York, NY 10029 USA

[12] Mt Sinai Sch Med, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA

[13] Mt Sinai Sch Med, Inst Genom & Multiscale Biol, Dept Genet & Genom Sci, New York, NY 10029 USA

[14] Mt Sinai Sch Med, Dept Psychiat, Div Psychiat Genom, New York, NY 10029 USA

[15] Mt Sinai Sch Med, Genet Obes & Related Metab Traits Program, Inst Child Hlth & Dev, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA

[16] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA

[17] Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA

[18] Univ Penn, Sch Med, Dept Pediat, Philadelphia, PA 19104 USA

[19] Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA

[20] Univ Med Ctr Rotterdam, Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands

[21] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Rheumatol Immunol & Allergy, Boston, MA 02115 USA

[22] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Genet, Boston, MA 02115 USA

[23] RIKEN, CGM, Lab Genotyping Dev, Yokohama, Kanagawa, Japan

[24] Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, Chicago, IL 60611 USA

[25] Univ N Carolina, Neurogenet Lab, Chapel Hill, NC 27599 USA

[26] Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA

[27] NIA, Hlth Dispar Res Sect, Clin Res Branch, NIH, Baltimore, MD 21225 USA

[28] NHLBI, Div Cardiovasc Sci, Bethesda, MD 20892 USA

[29] NIA, Lab Personal & Cognit, NIH, Baltimore, MD 21224 USA

[30] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA

[31] Univ Michigan Hlth Syst, Div Cardiol, Ann Arbor, MI 48109 USA

[32] Harvard Univ, Sch Med, Dept Genet, Cambridge, MA 02138 USA

[33] Broad Inst MIT & Harvard, Cambridge, MA 02141 USA

[34] Univ Mississippi, Med Ctr, Dept Physiol & Biophys, Jackson, MS 39216 USA

[35] Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada

[36] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA

来源：

HUMAN MOLECULAR GENETICS | 2013年 / 22卷 / 12期

关键词：

ERYTHROID PROGENITORS; ALPHA-THALASSEMIA; HEMOGLOBIN LEVELS; IRON-DEFICIENCY; DIFFERENTIATION; GENE; HEMOCHROMATOSIS; INDIVIDUALS; CONSORTIUM; EXPRESSION;

D O I：

10.1093/hmg/ddt087

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 1E13 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.

引用

页码：2529 / 2538

页数：10

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