Genome-wide Association and Population Genetic Analysis of C-Reactive Protein in African American and Hispanic American Women
Genome-wide Association and Population Genetic Analysis of C-Reactive Protein in African American and Hispanic American Women
复制标题
DOI：
10.1016/j.ajhg.2012.07.023
复制
发表时间：
2012-09-07
影响因子：
9.8
通讯作者：
Tang, Hua
中科院分区：
文献类型：
--
作者：
Reiner, Alex P.;Beleza, Sandra;Tang, Hua
C反应蛋白(CRP)是一种全身性炎症标记物，可预测未来的心血管风险。非裔美国人和西班牙裔美国人的CRP水平高于欧洲裔美国人，但在这些混杂的美国少数民族中，CRP的基因决定因素很大程度上是未知的。我们对来自妇女健康倡议SNP健康协会资源的8,280名非裔美国人(AA)和3,548名西班牙裔美国人(HA)绝经后妇女进行了全基因组关联研究(GWAS)。我们在染色体6p21(p=10(-10))区域发现并验证了一种C反应蛋白相关的由髓样细胞表达的受体(TREM2)的变体。与较高的CRP相关的TREM2变异在非洲很常见，但在其他祖先群体中很少见。在AA妇女中，1q23的CRP区域包含一个强烈的混合关联信号(p=10(-17))，似乎与几个独立的CRP相关等位基因有关；其中最强的等位基因仅存在于非洲祖先人群中，并与较高的CRP相关。在欧洲人群中以前通过GWAS与CRP相关的其他基因组基因座中，大多数基因座(LEPR、IL1RN、IL6R、GCKR、NLRP3、HNF1A、HNF4a和APOC1)在AA和HA女性中显示出与CRP一致的关联模式。综上所述，我们在美国少数民族人群中发现了一种常见的与CRP相关的TREM2变异。再生障碍性贫血妇女的CRP表型的遗传结构是复杂的，涉及不同群体之间共享的遗传变异，以及非洲裔群体特有的变异。
C-reactive protein (CRP) is a systemic inflammation marker that predicts future cardiovascular risk. CRP levels are higher in African Americans and Hispanic Americans than in European Americans, but the genetic determinants of CRP in these admixed United States minority populations are largely unknown. We performed genome-wide association studies (GWASs) of 8,280 African American (AA) and 3,548 Hispanic American (HA) postmenopausal women from the Women's Health Initiative SNP Health Association Resource. We discovered and validated a CRP-associated variant of triggering receptors expressed by myeloid cells 2 (TREM2) in chromosomal region 6p21 (p = 10(-10)). The TREM2 variant associated with higher CRP is common in Africa but rare in other ancestral populations. In AA women, the CRP region in 1q23 contained a strong admixture association signal (p = 10(-17)), which appears to be related to several independent CRP-associated alleles; the strongest of these is present only in African ancestral populations and is associated with higher CRP. Of the other genomic loci previously associated with CRP through GWASs of European populations, most loci (LEPR, IL1RN, IL6R, GCKR, NLRP3, HNF1A, HNF4A, and APOC1) showed consistent patterns of association with CRP in AA and HA women. In summary, we have identified a common TREM2 variant associated with CRP in United States minority populations. The genetic architecture underlying the CRP phenotype in AA women is complex and involves genetic variants shared across populations, as well as variants specific to populations of African descent.