Genetic association analysis highlights new loci that modulate hematological trait variation in Caucasians and African Americans.
Genetic association analysis highlights new loci that modulate hematological trait variation in Caucasians and African Americans.
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DOI：
10.1007/s00439-010-0925-1
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发表时间：
2011-03
期刊：
影响因子：
5.3
通讯作者：
Lettre G
中科院分区：
文献类型：
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作者：
Lo KS;Wilson JG;Lange LA;Folsom AR;Galarneau G;Ganesh SK;Grant SF;Keating BJ;McCarroll SA;Mohler ER 3rd;O'Donnell CJ;Palmas W;Tang W;Tracy RP;Reiner AP;Lettre G
红细胞、白色细胞和血小板测量，包括它们的计数、亚型和体积，是几种人类疾病的重要诊断和预后临床参数。为了确定与血液学性状相关的新基因座，并比较不同种族之间这些表型的结构，CARe项目对来自5个基于人群的队列的23，439名高加索人和7，112名非洲裔美国人的DNA中约2，100个候选基因的变异进行了49，094个单核苷酸多态性（SNP）基因分型。我们发现非裔美国人的红细胞表型和葡萄糖-6磷酸脱氢酶（G6 PD）A等位基因之间有很强的新关联（rs 1050828，P < 2.0 × 10 - 13，T等位基因与较低的红细胞计数、血红蛋白和红细胞压积以及较高的平均红细胞体积相关），以及血小板计数与原肌球蛋白-4（TPM 4）位点SNP之间的关系（rs 8109288，白人P = 3.0 × 10−7;非裔美国人P = 3.0 × 10−7，T等位基因与血小板计数降低相关）。我们强烈地复制了许多遗传协会血细胞表型先前建立在高加索人。在非裔美国人中，α-珠蛋白（HBA 2-HBA 1）基因座的一种常见变异与红细胞性状相关，但在高加索人中则不相关（rs 1211375，P < 7 × 10−8，A等位基因与较低的血红蛋白、平均红细胞血红蛋白和平均红细胞体积相关）。我们的研究结果显示了欧洲和非洲来源的人群中血液学性状遗传调控的相似性，但也存在差异，并强调了自然选择在塑造这些差异中的作用。
Red blood cell, white blood cell, and platelet measures, including their count, sub-type and volume, are important diagnostic and prognostic clinical parameters for several human diseases. To identify novel loci associated with hematological traits, and compare the architecture of these phenotypes between ethnic groups, the CARe Project genotyped 49,094 single nucleotide polymorphisms (SNPs) that capture variation in ~2,100 candidate genes in DNA of 23,439 Caucasians and 7,112 African Americans from five population-based cohorts. We found strong novel associations between erythrocyte phenotypes and the glucose-6 phosphate dehydrogenase (G6PD) A-allele in African Americans (rs1050828, P < 2.0 × 10−13, T-allele associated with lower red blood cell count, hemoglobin, and hematocrit, and higher mean corpuscular volume), and between platelet count and a SNP at the tropomyosin-4 (TPM4) locus (rs8109288, P = 3.0 × 10−7 in Caucasians; P = 3.0 × 10−7 in African Americans, T-allele associated with lower platelet count). We strongly replicated many genetic associations to blood cell phenotypes previously established in Caucasians. A common variant of the α-globin (HBA2-HBA1) locus was associated with red blood cell traits in African Americans, but not in Caucasians (rs1211375, P < 7 × 10−8, A-allele associated with lower hemoglobin, mean corpuscular hemoglobin, and mean corpuscular volume). Our results show similarities but also differences in the genetic regulation of hematological traits in European- and African-derived populations, and highlight the role of natural selection in shaping these differences.
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影响因子：
6.5
作者：
Nouraie M;Reading NS;Campbell A;Minniti CP;Rana SR;Luchtman-Jones L;Kato GJ;Gladwin MT;Castro OL;Prchal JT;Gordeuk VR
通讯作者：
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