Mahaney M C, Blangero J, Rainwater D L, Comuzzie A G, VandeBerg J L, Stern M P, MacCluer J W, Hixson J E
Department of Genetics, Southwest Foundation for Biomedical Research, San Antonio, TX 78228-0147, USA.
Arterioscler Thromb Vasc Biol. 1995 Oct;15(10):1730-9. doi: 10.1161/01.atv.15.10.1730.
To detect and measure the effects of a single locus on quantitative variation in plasma concentrations of HDL cholesterol (HDL-C), we conducted statistical genetic analyses on data from 526 Mexican American individuals in 25 randomly ascertained pedigrees. By using maximum-likelihood complex segregation analysis, we found evidence for a major locus with a codominant mixture model that included the phenotypic means, standard deviations, relative frequency of a low HDL-C allele, and heritability for plasma HDL-C levels, plus the effects of sex (genotype specific), age-by-sex, age2-by-sex, plasma concentrations of apolipoprotein (apo)AI and triglycerides (genotype specific), exogenous sex hormone use, and menopausal status under an unrestricted general model. Inclusion of the four covariates (in addition to the sex and age-by-sex effects) accounted for nearly 79% of the variance in total plasma HDL-C levels. Of the remaining 21% of the variance, the detected major locus accounted for approximately 55% in men and 21% in women; the total genetic contributions to the variance by genes were approximately 82% in men and 69% in women. Linkage analyses with penetrance parameter estimates from the segregation analysis excluded tight linkage between the detected major locus and markers for the following candidate loci: the apoAI/apoCIII genomic region (P < .05), apoB (P < .01), hepatic lipase (P < .001), lipoprotein lipase (P < .001), and the LDL receptor (P < .001). While not excluding the apoE locus (LOD = -0.348, P < .21), the analysis provided no support for tight linkage between it and the detected major locus.
为了检测和测量单个基因座对高密度脂蛋白胆固醇（HDL-C）血浆浓度定量变异的影响，我们对来自25个随机确定的家系中的526名墨西哥裔美国人的数据进行了统计遗传分析。通过使用最大似然复杂分离分析，我们发现了一个主要基因座的证据，该基因座具有共显性混合模型，其中包括表型均值、标准差、低HDL-C等位基因的相对频率以及血浆HDL-C水平的遗传力，再加上性别（基因型特异性）、年龄×性别、年龄²×性别、载脂蛋白（apo）AI和甘油三酯的血浆浓度（基因型特异性）、外源性性激素使用以及在无限制一般模型下的绝经状态的影响。纳入四个协变量（除性别和年龄×性别效应外）占血浆总HDL-C水平变异的近79%。在其余21%的变异中，检测到的主要基因座在男性中占约55%，在女性中占21%；基因对变异的总遗传贡献在男性中约为82%，在女性中约为69%。使用来自分离分析的外显率参数估计进行的连锁分析排除了检测到的主要基因座与以下候选基因座的标记之间的紧密连锁：apoAI/apoCIII基因组区域（P <.05）、apoB（P <.01）、肝脂酶（P <.001）、脂蛋白脂酶（P <.001）和低密度脂蛋白受体（P <.001）。虽然不排除载脂蛋白E基因座（LOD = -0.348，P <.21），但该分析没有为其与检测到的主要基因座之间的紧密连锁提供支持。
