Admixture mapping of white cell count: Genetic locus responsible for lower white blood cell count in the health ABC and Jackson Heart Studies
Admixture mapping of white cell count: Genetic locus responsible for lower white blood cell count in the health ABC and Jackson Heart Studies
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DOI：
10.1016/j.ajhg.2007.09.003
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发表时间：
2008-01-01
影响因子：
9.8
通讯作者：
Ziv, Elad
中科院分区：
文献类型：
--
作者：
Nalls, Michael A.;Wilson, James G.;Ziv, Elad
白细胞计数（WBC）是一项重要的临床指标，在不同民族之间存在差异。众所周知，非洲裔美国人的白细胞比欧洲裔美国人低。我们用混合作图法调查了整个基因组中导致白细胞差异的位点。我们分析了来自非裔美国人健康、衰老和身体成分研究和杰克逊心脏研究参与者的数据。两项研究的参与者都通过b> = 1322个单核苷酸多态性进行了基因分型，这些多态性是预先选择的，可以为非洲和欧洲血统提供信息，并且跨越整个基因组。我们使用这些标记来估计每个染色体区域的遗传祖先，然后测试白细胞与每个位点遗传祖先之间的关联。我们发现染色体1q上的一个位点与WBC密切相关（P < 10(-12)）。最强的相关性与已知影响达菲血型抗原表达的标记物有关。具有两个西非常见等位基因拷贝的参与者的平均WBC为4.9 (SD 1.3)；同时携带欧洲常见等位基因的参与者的平均白细胞为7.1 （SD为1.3）。这种变异解释了大约20%的白细胞群体变异。我们使用混合定位，一种进行遗传关联研究的新方法，找到了染色体1q上与白细胞显著相关的区域。需要进一步的研究来确定这种效应的生物学机制及其临床意义。
White blood cell count (WBC) is an important clinical marker that varies among different ethnic groups. African Americans are known to have a lower WBC than European Americans. We surveyed the entire genome for loci underlying this difference in WBC by using admixture mapping. We analyzed data from African American participants in the Health, Aging, and Body Composition Study and the Jackson Heart Study. Participants of both studies were genotyped across >= 1322 single nucleotide polymorphisms that were preselected to be informative for African versus European ancestry and span the entire genome. We used these markers to estimate genetic ancestry in each chromosomal region and then tested the association between WBC and genetic ancestry at each locus. We found a locus on chromosome 1q strongly associated with WBC (P < 10(-12)). The strongest association was with a marker known to affect the expression of the Duffy blood group antigen. Participants who had both copies of the common West African allele had a mean WBC of 4.9 (SD 1.3); participants who had both common European alleles had a mean WBC of 7.1 (SD 1.3). This variant explained similar to 20% of population variation in WBC. We used admixture mapping, a novel method for conducting genetic-association studies, to find a region that was significantly associated with WBC on chromosome 1q. Additional studies are needed to determine the biological mechanism for this effect and its clinical implications.