Rice T, Sprecher D L, Borecki I B, Mitchell L E, Laskarzewski P M, Rao D C
Washington University School of Medicine, Division of Biostatistics, St Louis, MO 63110.
Metabolism. 1993 Oct;42(10):1284-90. doi: 10.1016/0026-0495(93)90126-9.
Dehydroepiandrosterone sulfate (DHEAS) was examined in random (control) and nonrandom (case) families participating in the Cincinnati Myocardial Infarction and Hormone (CIMIH) family study. The case families were ascertained through white men who survived a myocardial infarction (MI) before the age of 56, whereas control families were recruited through advertisements and through an adolescent boy maturation study. Both familial correlations and genetic effects of DHEAS were investigated. First, maximum likelihood estimates of the sex-specific familial correlations (corrected for nonrandom ascertainment) suggested that there was significant heterogeneity between the two sampling types. This heterogeneity was isolated to the male sibling correlation, which was higher in the case than control families. Post hoc analyses suggested that the sibling group heterogeneity may be in part a function of age, since the control sample offspring were on average much younger than those in case families. No sex differences other than those for the siblings were noted in the familial correlations. Second, heritability was investigated in control families using a simple path model (TAU) that allowed for sex differences. The only significant model parameter was the sex-specific familiarity (combined polygenic and familial environmental effects), which was larger in females (74%) than in males (29%). In general, these analyses suggested that (1) DHEAS may play only a limited role in the increased risk for premature MI, and (2) the degree of heritable (familial) variation may be dependent on sex.
在参与辛辛那提心肌梗死与激素(CIMIH)家族研究的随机(对照)和非随机(病例)家族中,对硫酸脱氢表雄酮(DHEAS)进行了检测。病例家族是通过56岁之前经历过心肌梗死(MI)且存活下来的白人男性确定的,而对照家族则是通过广告以及一项青少年男孩发育研究招募的。对DHEAS的家族相关性和遗传效应均进行了研究。首先,对性别特异性家族相关性(针对非随机确定进行校正)的最大似然估计表明,两种抽样类型之间存在显著的异质性。这种异质性仅限于男性同胞相关性,病例家族中的该相关性高于对照家族。事后分析表明,同胞组异质性可能部分是年龄的函数,因为对照样本的后代平均比病例家族中的后代年轻得多。在家族相关性方面,除了同胞的情况外,未发现其他性别差异。其次,在对照家族中使用允许性别差异的简单路径模型(TAU)研究了遗传力。唯一显著的模型参数是性别特异性的相似性(综合多基因和家族环境效应),女性(74%)高于男性(29%)。总体而言,这些分析表明:(1)DHEAS在过早发生MI的风险增加中可能仅起有限作用;(2)可遗传(家族性)变异的程度可能取决于性别。