Mahaney M C, Blangero J, Comuzzie A G, VandeBerg J L, Stern M P, MacCluer J W
Department of Genetics, Southwest Foundation for Biomedical Research, San Antonio, TX 78228-0147, USA.
Circulation. 1995 Dec 1;92(11):3240-8. doi: 10.1161/01.cir.92.11.3240.
The conjoint trait hypothesis proposes that combined low HDL cholesterol (HDL-C) and high triglyceride (TG) levels represent a single, inherited phenotype that adiposity may influence in an unspecified manner. We conducted formal statistical genetic tests of the conjoint trait hypothesis and the relation of the conjoint trait to adiposity using data for 569 subjects in 25 pedigrees from the San Antonio Family Heart Study.
We conducted multivariate genetic analyses to detect the effects of genes and environmental factors on variation in plasma concentrations of HDL-C and TG, fat mass (as percent body weight [FM%], determined by bioelectric impedance), and body mass index (BMI). We used maximum-likelihood methods to simultaneously estimate the phenotypic means and SDs, heritabilities (h2), effects of sex, age-by-sex, eight dietary and medical covariates, and genetic and environmental correlations. Likelihood ratio tests disclosed significant heritabilities (P < .001) for all traits (h2HDL-C = 0.55, h2TG = 0.53, h2FM% = 0.37, h2BMI = 0.44) but significant genetic correlations (P < .001), indicating pleiotropy, between two trait pairs only: HDL-C and TG (PG = -0.52) and fat mass and BMI (PG = 0.86). We obtained significant environmental correlations between all trait pairs except HDL-C and BMI (P > .05).
Both shared genes (pleiotropy) and shared environmental factors contribute to the commonly observed inverse phenotypic association between plasma levels of HDL-C and TG. Rather than low HDL-C and high TG being a single, genetically transmissible entity, it is the inverse relation between these two phenotypes throughout their normal ranges of variation as well as at the extremes that is influenced by shared genes and shared environments. However, common environmental factors, not shared genes, account for reported associations of plasma HDL-C and TG levels with measures of adiposity.
联合性状假说提出，低高密度脂蛋白胆固醇（HDL-C）和高甘油三酯（TG）水平的组合代表一种单一的遗传表型，肥胖可能以一种未明确的方式对其产生影响。我们使用圣安东尼奥家族心脏研究中25个家系的569名受试者的数据，对联合性状假说以及联合性状与肥胖的关系进行了正式的统计遗传学检验。
我们进行了多变量遗传分析，以检测基因和环境因素对HDL-C、TG血浆浓度、脂肪量（以生物电阻抗测定的体重百分比[FM%]表示）和体重指数（BMI）变异的影响。我们使用最大似然法同时估计表型均值和标准差、遗传力（h2）、性别效应、性别与年龄的交互效应、八个饮食和医学协变量，以及遗传和环境相关性。似然比检验显示所有性状均具有显著的遗传力（P <.001）（h2HDL-C = 0.55，h2TG = 0.53，h2FM% = 0.37，h2BMI = 0.44），但仅在两个性状对之间存在显著的遗传相关性（P <.001），表明存在多效性：HDL-C和TG（PG = -0.52）以及脂肪量和BMI（PG = 0.86）。我们在除HDL-C和BMI之外的所有性状对之间均获得了显著的环境相关性（P >.05）。
共享基因（多效性）和共享环境因素均导致血浆HDL-C和TG水平之间常见的反向表型关联。并非低HDL-C和高TG是一个单一的、可遗传传递的实体，而是这两种表型在其整个正常变异范围内以及极端情况下的反向关系受到共享基因和共享环境的影响。然而，血浆HDL-C和TG水平与肥胖指标之间已报道的关联是由共同环境因素而非共享基因导致的。
