GWAS of blood cell traits identifies novel associated loci and epistatic interactions in Caucasian and African-American children

被引：77

作者：

Li, Jin ^{[1
]}

Glessner, Joseph T. ^{[1
]}

Zhang, Haitao ^{[1
]}

Hou, Cuiping ^{[1
]}

Wei, Zhi ^{[3
]}

Bradfield, Jonathan P. ^{[1
]}

Mentch, Frank D. ^{[1
]}

Guo, Yiran ^{[1
]}

Kim, Cecilia ^{[1
]}

Xia, Qianghua ^{[2
]}

Chiavacci, Rosetta M. ^{[1
]}

Thomas, Kelly A. ^{[1
]}

Qiu, Haijun ^{[1
]}

Grant, Struan F. A. ^{[1
,2
,4
]}

Furth, Susan L. ^{[4
]}

Hakonarson, Hakon ^{[1
,2
,4
]}

Sleiman, Patrick M. A. ^{[1
,2
,4
]}

机构：

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

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

[3] New Jersey Inst Technol, Dept Comp Sci, Newark, NJ 07102 USA

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

来源：

HUMAN MOLECULAR GENETICS | 2013年 / 22卷 / 07期

关键词：

GENOME-WIDE ASSOCIATION; IRON-DEFICIENCY ANEMIA; MUTATIONS; IRIDA; METAANALYSIS; POPULATION; CONSORTIUM; VARIANT; COUNT;

D O I：

10.1093/hmg/dds534

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：

Hematological traits are important clinical indicators, the genetic determinants of which have not been fully investigated. Common measures of hematological traits include red blood cell (RBC) count, hemoglobin concentration (HGB), hematocrit (HCT), mean corpuscular hemoglobin (MCH), MCH concentration (MCHC), mean corpuscular volume (MCV), platelet count (PLT) and white blood cell (WBC) count. We carried out a genome-wide association study of the eight common hematological traits among 7943 African-American children and 6234 Caucasian children. In African Americans, we report five novel associations of HBE1 variants with HCT and MCHC, the alpha-globin gene cluster variants with RBC and MCHC, and a variant at the ARHGEF3 locus with PLT, as well as replication of four previously reported loci at genome-wide significance. In Caucasians, we report a novel association of variants at the COPZ1 locus with PLT as well as replication of four previously reported loci at genome-wide significance. Extended analysis of an association observed between MCH and the alpha-globin gene cluster variants demonstrated independent effects and epistatic interaction at the locus, impacting the risk of iron deficiency anemia in African Americans with specific genotype states. In summary, we extend the understanding of genetic variants underlying hematological traits based on analyses in African-American children.

引用

页码：1457 / 1464

页数：8

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