Association studies of vascular phenotypes: how and why?
Association studies of vascular phenotypes: how and why?
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DOI：
10.1161/01.atv.0000024686.49995.41
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发表时间：
2002-07
期刊：
影响因子：
--
通讯作者：
L. Almasy;J. Maccluer
中科院分区：
文献类型：
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作者：
L. Almasy;J. Maccluer
过去十年的技术和方法进步使得对复杂性状的遗传学研究变得越来越可行，这些性状受多个基因及其相互之间以及与环境的相互作用的影响。心血管疾病及其危险因素一直是众多遗传学研究的主题，旨在确定影响这些特征的特定 DNA 变异。一项此类研究发表在本期《动脉硬化、血栓形成和血管生物学》中。 Brousseau 及其同事1 研究了胆固醇酯转移蛋白 (CETP) 基因中的一个变体与脂质和脂蛋白浓度、颗粒大小和冠心病终点的关联。鉴于遗传关联研究在期刊中出现的频率不断增加，我们借此机会解释这些研究中使用的方法类型、如何解释这些研究的结果，以及关联技术如何适应更大的遗传流行病学方法。请参见第 1148 页 遗传关联研究本质上是寻找表型和基因型之间的相关性。表型可以是是否存在疾病，例如动脉粥样硬化，也可以是定量测量，例如收缩压或高密度脂蛋白胆固醇浓度。下面解释的略有不同的分析技术用于离散和定量表型。基因型通常是从某种类型的多态性标记获得的。这可能是短串联重复或微卫星，其中 2、3 或 4 碱基对 DNA 基序的拷贝数在群体中发生变化，也可能是单核苷酸多态性 (SNP)，其中特定 DNA 碱基对发生变化。如果最常见变体的频率低于 99%，则称标记具有多态性并且可称为多态性。微卫星通常有 4 到 12 个变体或等位基因，而 SNP 通常有……
Technological and methodological advances in the last decade have rendered genetic studies of complex traits, influenced by multiple genes and their interactions with each other and with the environment, increasingly feasible. Cardiovascular disease and its risk factors have been the subject of numerous genetic studies seeking to identify the specific DNA variants that influence these traits. One such study appears in this issue of Arteriosclerosis, Thrombosis, and Vascular Biology . Brousseau and colleagues1 investigate associations of a variant in the cholesteryl ester transfer protein (CETP) gene with lipid and lipoprotein concentrations, particle sizes, and coronary heart disease endpoints. Given the increasing frequency of genetic association studies in the pages of the Journal, we take this opportunity to explain the types of methodology used in these studies, how the results of these studies may be interpreted, and how association techniques fit into the larger arsenal of genetic epidemiological methods. See page 1148 Genetic association studies essentially look for correlations between phenotype and genotype. The phenotype may be presence or absence of disease, such as atherosclerosis, or it may be a quantitative measure such as systolic blood pressure or HDL cholesterol concentration. Slightly different analytical techniques, explained below, are used for discrete and quantitative phenotypes. The genotype is generally obtained from some type of polymorphic marker. This may be a short tandem repeat or microsatellite in which the number of copies of a 2-, 3-, or 4-base pair DNA motif varies in the population or it may be a single nucleotide polymorphism (SNP) in which a particular DNA base pair varies. A marker is said to be polymorphic and may be referred to as a polymorphism, if the frequency of the most common variant is less than 99%. Microsatellites generally have 4 to 12 variants, or alleles, whereas SNPs generally have …