GWAS of blood cell traits identifies novel associated loci and epistatic interactions in Caucasian and African-American children
GWAS of blood cell traits identifies novel associated loci and epistatic interactions in Caucasian and African-American children
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DOI：
10.1093/hmg/dds534
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发表时间：
2013-04-01
影响因子：
3.5
通讯作者：
Sleiman, Patrick M. A.
中科院分区：
文献类型：
--
作者：
Li, Jin;Glessner, Joseph T.;Sleiman, Patrick M. A.
血液学性状是重要的临床指标，其遗传决定因素尚未得到充分研究。血液学特征的常见指标包括红细胞（RBC）计数、血红蛋白浓度（HGB）、红细胞压积（HCT）、平均红细胞血红蛋白（MCH）、MCH浓度（MCHC）、平均红细胞体积（MCV）、血小板计数（PLT）和白色血细胞（WBC）计数。我们对7943名非洲裔美国儿童和6234名白人儿童的8种常见血液学性状进行了全基因组关联研究。在非裔美国人中，我们报告了5种新的HBE 1变异与HCT和MCHC的关联，α-珠蛋白基因簇变异与RBC和MCHC的关联，ARHGEF 3基因座变异与PLT的关联，以及4个先前报道的基因座在全基因组意义上的复制。在高加索人中，我们报告了一种新的关联的COPZ 1基因座与PLT的变异，以及复制的四个先前报告的基因座在全基因组的意义。对MCH和α-珠蛋白基因簇变异体之间观察到的关联的扩展分析表明，在该位点存在独立效应和上位相互作用，影响具有特定基因型状态的非裔美国人患缺铁性贫血的风险。总之，我们基于对非裔美国儿童的分析，扩展了对血液学特征相关遗传变异的理解。
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.