Tiret L, André J L, Ducimetière P, Herbeth B, Rakotovao R, Guegen R, Spyckerelle Y, Cambien F
Institut National de la Santé et de la Recherche Médicale (INSERM) U258, Hôpital Broussais, Paris, France.
Genet Epidemiol. 1992;9(6):389-403. doi: 10.1002/gepi.1370090603.
A segregation analysis using a regressive model with generation- and age-dependent effects was applied to familial data of height-adjusted weight to investigate the major gene hypothesis. The sample included 629 nuclear families with 2,534 members volunteering for a free health check-up in the Preventive Medicine Center of Vandoeuvre-lès-Nancy, France. The familial correlations were 0.094 +/- 0.040 between spouses, 0.198 +/- 0.023 between parent and offspring, and 0.327 +/- 0.034 between siblings. The variability of the trait was higher in parents than in offspring. The most parsimonious genetic model indicated a codominant major effect increasing with age in childhood, then stabilizing in adulthood. The same data were analyzed using the classical mixed model, assuming equality of variances between parents and offspring, no resemblance between spouses, similar parent-offspring and sib-sib correlations, and identical effects in parents and offspring. This analysis indicated a recessive solution. In both analyses, mendelian transmission was rejected. However, the mixture of two distributions in the recessive model, instead of three in the codominant one, was less constraining with respect to the test of transmission probabilities, and the rejection of mendelian transmission was due to a single family in the recessive case, instead of several families in the codominant one. This could possibly explain why previous studies, all using the mixed model, found evidence for a recessive major gene. Although the major gene hypothesis cannot be definitely ruled out from our results, the mechanism appears more complex than the effect of one single gene.
采用具有代际和年龄依赖性效应的回归模型对身高调整体重的家族数据进行分离分析，以研究主基因假说。样本包括629个核心家庭，共2534名成员，他们在法国南锡附近万德uvre的预防医学中心自愿参加免费健康检查。配偶之间的家族相关性为0.094±0.040，父母与后代之间为0.198±0.023，兄弟姐妹之间为0.327±0.034。该性状的变异性在父母中比在后代中更高。最简约的遗传模型表明，一个共显性主效应在儿童期随年龄增加，然后在成年期稳定。使用经典混合模型对相同数据进行分析，假设父母与后代之间方差相等，配偶之间无相似性，父母与后代以及兄弟姐妹之间的相关性相似，且父母与后代的效应相同。该分析表明是隐性遗传模式。在两种分析中，孟德尔遗传均被拒绝。然而，隐性模型中两种分布的混合，而非共显性模型中的三种分布，在传递概率检验方面限制较小，并且在隐性情况下孟德尔遗传的拒绝是由于单个家庭，而非共显性情况下的几个家庭。这可能解释了为什么以前所有使用混合模型的研究都发现了隐性主基因的证据。尽管从我们的结果中不能绝对排除主基因假说，但该机制似乎比单个基因的效应更为复杂。
